How to make a midbrain dopaminergic neuron

Development (Cambridge)

Volumn 142, Issue 11, 2015, Pages 1918-1936

  Arenas, Ernest ^a   Denham, Mark ^a,b   Villaescusa, J Carlos ^a,c  

^a KAROLINSKA INSTITUTE   (Sweden)

^b AARHUS UNIVERSITY   (Denmark)

^c MASARYK UNIVERSITY   (Czech Republic)

Author keywords

Dopamine neurons; Midbrain; Parkinson s disease; Regeneration; Reprogramming; Stem cells

Indexed keywords

TRANSCRIPTION FACTOR;

ARTICLE; CELL FATE; CELL MIGRATION; CELL SURVIVAL; DOPAMINERGIC NERVE CELL; HUMAN; MESENCEPHALON; NERVE CELL DIFFERENTIATION; NERVOUS SYSTEM DEVELOPMENT; NEUROBLAST; NONHUMAN; NUCLEAR REPROGRAMMING; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; SOMATIC CELL; TRANSCRIPTION REGULATION; ANIMAL; BIOLOGICAL MODEL; CYTOLOGY; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MORPHOGENESIS;

ANIMALS; BODY PATTERNING; DOPAMINERGIC NEURONS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMANS; MESENCEPHALON; MODELS, BIOLOGICAL; NEUROGENESIS;

EID: 84929884392     PISSN: 09501991     EISSN: 14779129     Source Type: Journal    
DOI: 10.1242/dev.097394     Document Type: Article

References (277)

1. Addis, R. C., Hsu, F.-C., Wright, R. L., Dichter, M. A., Coulter, D. A. and Gearhart, J. D. (2011). Efficient conversion of astrocytes to functional midbrain dopaminergic neurons using a single polycistronic vector. PLoS ONE 6, e28719.
2. Agid, Y., Taquet, H., Cesselin, F., Epelbaum, J. and Javoy-Agid, F. (1986). Neuropeptides and Parkinson’s disease. Prog. Brain Res. 66, 107-116.
3. Akerud, P., Alberch, J., Eketjäll, S., Wagner, J. and Arenas, E. (1999). Differential effects of glial cell line-derived neurotrophic factor and neurturin on developing and adult substantia nigra dopaminergic neurons. J. Neurochem. 73, 70-78.
4. Akerud, P., Canals, J. M., Snyder, E. Y. and Arenas, E. (2001). Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model of Parkinson’s disease. J. Neurosci. 21, 8108-8118.
5. Akerud, P., Holm, P. C., Castelo-Branco, G., Sousa, K., Rodriguez, F. J. and Arenas, E. (2002). Persephin-overexpressing neural stem cells regulate the function of nigral dopaminergic neurons and prevent their degeneration in a model of Parkinson’s disease. Mol. Cell. Neurosci. 21, 205-222.
6. Almqvist, P. M., Åkesson, E., Wahlberg, L. U., Pschera, H., Seiger, Å. and Sundström, E. (1996). First trimester development of the human nigrostriatal dopamine system. Exp. Neurol. 139, 227-237.
7. Alvarez-Fischer, D., Fuchs, J., Castagner, F., Stettler, O., Massiani-Beaudoin, O., Moya, K. L., Bouillot, C., Oertel, W. H., Lombès, A., Faigle, W. et al. (2011). Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex I insults. Nat. Neurosci. 14, 1260-1266.
8. Ambasudhan, R., Talantova, M., Coleman, R., Yuan, X., Zhu, S., Lipton, S. A. and Ding, S. (2011). Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell 9, 113-118.
9. Andersson, E., Jensen, J. B., Parmar, M., Guillemot, F. and Björklund, A. (2006a). Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2. Development 133, 507-516.
10. Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., Perlmann, T. and Ericson, J. (2006b). Identification of intrinsic determinants of midbrain dopamine neurons. Cell 124, 393-405.
11. Andersson, E. R., Prakash, N., Cajanek, L., Minina, E., Bryja, V., Bryjova, L., Yamaguchi, T. P., Hall, A. C., Wurst, W. and Arenas, E. (2008). Wnt5a regulates ventral midbrain morphogenesis and the development of A9-A10 dopaminergic cells in vivo. PLoS ONE 3, e3517.
12. Andersson, E. R., Salto, C., Villaescusa, J. C., Cajanek, L., Yang, S., Bryjova, L., Nagy, I. I., Vainio, S. J., Ramirez, C., Bryja, V. et al. (2013). Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells. Proc. Natl. Acad. Sci. USA 110, E602-E610.
13. Ang, S.-L. and Rossant, J. (1994). HNF-3 beta is essential for node and notochord formation in mouse development. Cell 78, 561-574.
14. Ang, S. L., Wierda, A., Wong, D., Stevens, K. A., Cascio, S., Rossant, J. and Zaret, K. S. (1993). The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development 119, 1301-1315.
15. Arenas, E. (2010). Towards stem cell replacement therapies for Parkinson’s disease. Biochem. Biophys. Res. Commun. 396, 152-156.
16. Arenas, E. (2014). Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson’s disease. J. Mol. Cell Biol. 6, 42-53.
17. Arenas, E., Trupp, M., Åkerud, P. and Ibańḛz, C. F. (1995). GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo. Neuron 15, 1465-1473.
18. Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., McLauchlan, H., Klevernic, I., Arthur, J. S. C., Alessi, D. R. and Cohen, P. (2007). The selectivity of protein kinase inhibitors: a further update. Biochem. J. 408, 297-315.
19. Baquet, Z. C., Bickford, P. C. and Jones, K. R. (2005). Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J. Neurosci. 25, 6251-6259.
20. Basson, M. A., Echevarria, D., Ahn, C. P., Sudarov, A., Joyner, A. L., Mason, I. J., Martinez, S. and Martin, G. R. (2008). Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development. Development 135, 889-898.
21. Beck, K. D., Valverde, J., Alexi, T., Poulsen, K., Moffat, B., Vandlen, R. A., Rosenthal, A. and Hefti, F. (1995). Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain. Nature 373, 339-341.
22. Berninger, B., Costa, M. R., Koch, U., Schroeder, T., Sutor, B., Grothe, B. and Gotz, M. (2007). Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia. J. Neurosci. 27, 8654-8664.
23. Björklund, A. and Hökfelt, T. (1983). Handbook of Chemical Neuroanatomy. Amsterdam; New York: Elsevier.
24. Blaess, S., Bodea, G. O., Kabanova, A., Chanet, S., Mugniery, E., Derouiche, A., Stephen, D. and Joyner, A. L. (2011). Temporal-spatial changes in Sonic Hedgehog expression and signaling reveal different potentials of ventral mesencephalic progenitors to populate distinct ventral midbrain nuclei. Neural Dev. 6, 29.
25. Bodea, G. O., Spille, J.-H., Abe, P., Andersson, A. S., Acker-Palmer, A., Stumm, R., Kubitscheck, U. and Blaess, S. (2014). Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system. Development 141, 661-673.
26. Bonilla, S., Hall, A. C., Pinto, L., Attardo, A., Götz, M., Huttner, W. B. and Arenas, E. (2008). Identification of midbrain floor plate radial glia-like cells as dopaminergic progenitors. Glia 56, 809-820.
27. Brichta, L., Greengard, P. and Flajolet, M. (2013). Advances in the pharmacological treatment of Parkinson’s disease: targeting neurotransmitter systems. Trends Neurosci. 36, 543-554.
28. Briscoe, J. and Ericson, J. (1999). The specification of neuronal identity by graded Sonic Hedgehog signalling. Semin. Cell Dev. Biol. 10, 353-362.
29. Broccoli, V., Boncinelli, E. and Wurst, W. (1999). The caudal limit of Otx2 expression positions the isthmic organizer. Nature 401, 164-168.
30. Brown, A., Machan, J. T., Hayes, L. and Zervas, M. (2011). Molecular organization and timing of Wnt1 expression define cohorts of midbrain dopamine neuron progenitors in vivo. J. Comp. Neurol. 519, 2978-3000.
31. Byers, B., Cord, B., Nguyen, H. N., Schüle, B., Fenno, L., Lee, P. C., Deisseroth, K., Langston, J. W., Pera, R. R. and Palmer, T. D. (2011). SNCA triplication Parkinson’s patient’s iPSC-derived DA neurons accumulate alpha-synuclein and are susceptible to oxidative stress. PLoS ONE 6, e26159.
32. Caiazzo, M., Dell’Anno, M. T., Dvoretskova, E., Lazarevic, D., Taverna, S., Leo, D., Sotnikova, T. D., Menegon, A., Roncaglia, P., Colciago, G. et al. (2011). Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 476, 224-227.
33. Calabresi, P., Castrioto, A., Di Filippo, M. and Picconi, B. (2013). New experimental and clinical links between the hippocampus and the dopaminergic system in Parkinson’s disease. Lancet Neurol. 12, 811-821.
34. Carlsson, A. (2001). A half-century of neurotransmitter research: impact on neurology and psychiatry. Nobel lecture. Biosci. Rep. 21, 691-710.
35. Carlsson, T., Carta, M., Winkler, C., Bjorklund, A. and Kirik, D. (2007). Serotonin neuron transplants exacerbate L-DOPA-induced dyskinesias in a rat model of Parkinson’s disease. J. Neurosci. 27, 8011-8022.
36. Carlsson, T., Carta, M., Munoz, A., Mattsson, B., Winkler, C., Kirik, D. and Bjorklund, A. (2009). Impact of grafted serotonin and dopamine neurons on development of L-DOPA-induced dyskinesias in parkinsonian rats is determined by the extent of dopamine neuron degeneration. Brain 132, 319-335.
37. Castaño, J., Menendez, P., Bruzos-Cidon, C., Straccia, M., Sousa, A., Zabaleta, L., Vazquez, N., Zubiarrain, A., Sonntag, K.-C., Ugedo, L. et al. (2014). Fast and efficient neural conversion of human hematopoietic cells. Stem Cell Rep. 3, 1118-1131.
38. Castelo-Branco, G., Wagner, J., Rodriguez, F. J., Kele, J., Sousa, K., Rawal, N., Pasolli, H. A., Fuchs, E., Kitajewski, J. and Arenas, E. (2003). Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proc. Natl. Acad. Sci. USA 100, 12747-12752.
39. Castelo-Branco, G., Rawal, N. and Arenas, E. (2004). GSK-3beta inhibition/beta-catenin stabilization in ventral midbrain precursors increases differentiation into dopamine neurons. J. Cell Sci. 117, 5731-5737.
40. Castelo-Branco, G., Sousa, K. M., Bryja, V., Pinto, L., Wagner, J. and Arenas, E. (2006). Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion. Mol. Cell. Neurosci. 31, 251-262.
41. Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M. and Studer, L. (2009). Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat. Biotechnol. 27, 275-280.
42. Chanda, S., Ang, C. E., Davila, J., Pak, C., Mall, M., Lee, Q. Y., Ahlenius, H., Jung, S. W., Südhof, T. C. and Wernig, M. (2014). Generation of induced neuronal cells by the single reprogramming factor ASCL1. Stem Cell Rep. 3, 282-296.
43. Chao, J. and Nestler, E. J. (2004). Molecular neurobiology of drug addiction. Annu. Rev. Med. 55, 113-132.
44. Chaudhuri, K. R. and Schapira, A. H. V. (2009). Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 8, 464-474.
45. Chaudhuri, K. R., Healy, D. G. and Schapira, A. H. V. (2006). Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol. 5, 235-245.
46. Chi, C. L., Martinez, S., Wurst, W. and Martin, G. R. (2003). The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum. Development 130, 2633-2644.
47. Chiang, C., Litingtung, Y., Lee, E., Young, K. E., Corden, J. L., Westphal, H. and Beachy, P. A. (1996). Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407-413.
48. Choi-Lundberg, D. L., Lin, Q., Chang, Y.-N., Chiang, Y. L., Hay, C. M., Mohajeri, H., Davidson, B. L. and Bohn, M. C. (1997). Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 275, 838-841.
49. Chung, C. Y., Seo, H., Sonntag, K. C., Brooks, A., Lin, L. and Isacson, O. (2005a). Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection. Hum. Mol. Genet. 14, 1709-1725.
50. Chung, S., Hedlund, E., Hwang, M., Kim, D. W., Shin, B.-S., Hwang, D.-Y., Kang, U. J., Isacson, O. and Kim, K.-S. (2005b). The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neurons. Mol. Cell. Neurosci. 28, 241-252.
51. Chung, S., Leung, A., Han, B.-S., Chang, M.-Y., Moon, J.-I., Kim, C.-H., Hong, S., Pruszak, J., Isacson, O. and Kim, K.-S. (2009). Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway. Cell Stem Cell 5, 646-658.
52. Chung, C. Y., Khurana, V., Auluck, P. K., Tardiff, D. F., Mazzulli, J. R., Soldner, F., Baru, V., Lou, Y., Freyzon, Y., Cho, S. et al. (2013). Identification and rescue of alpha-synuclein toxicity in Parkinson patient-derived neurons. Science 342, 983-987.
53. Connolly, B. S. and Lang, A. E. (2014). Pharmacological treatment of Parkinson disease: a review. JAMA 311, 1670-1683.
54. Cooper, O., Seo, H., Andrabi, S., Guardia-Laguarta, C., Graziotto, J., Sundberg, M., McLean, J. R., Carrillo-Reid, L., Xie, Z., Osborn, T. et al. (2012). Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson’s disease. Sci. Transl. Med. 4, 141ra190.
55. Courtois, E. T., Castillo, C. G., Seiz, E. G., Ramos, M., Bueno, C., Liste, I. and Martinez-Serrano, A. (2010). In vitro and in vivo enhanced generation of human A9 dopamine neurons from neural stem cells by Bcl-XL. J. Biol. Chem. 285, 9881-9897.
56. Dahlstroem, A. and Fuxe, K. (1964). Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol. Scand. Suppl. 232, 231-255.
57. Davis, R. L., Weintraub, H. and Lassar, A. B. (1987). Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987-1000.
58. De la Rossa, A., Bellone, C., Golding, B., Vitali, I., Moss, J., Toni, N., Lüscher, C. and Jabaudon, D. (2013). In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons. Nat. Neurosci. 16, 193-200.
59. Decressac, M., Kadkhodaei, B., Mattsson, B., Laguna, A., Perlmann, T. and Bjorklund, A. (2012). alpha-Synuclein-induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons. Sci. Transl. Med. 4, 163ra156.
60. Dell’Anno, M. T., Caiazzo, M., Leo, D., Dvoretskova, E., Medrihan, L., Colasante, G., Giannelli, S., Theka, I., Russo, G., Mus, L. et al. (2014). Remote control of induced dopaminergic neurons in parkinsonian rats. J. Clin. Invest. 124, 3215-3229.
61. Demyanenko, G. P., Shibata, Y. and Maness, P. F. (2001). Altered distribution of dopaminergic neurons in the brain of L1 null mice. Brain Res. Dev. Brain Res. 126, 21-30.
62. Deng, Q., Andersson, E., Hedlund, E., Alekseenko, Z., Coppola, E., Panman, L., Millonig, J. H., Brunet, J.-F., Ericson, J. and Perlmann, T. (2011). Specific and integrated roles of Lmx1a, Lmx1b and Phox2a in ventral midbrain development. Development 138, 3399-3408.
63. Denham, M., Bye, C., Leung, J., Conley, B. J., Thompson, L. H. and Dottori, M. (2012). Glycogen synthase kinase 3beta and activin/nodal inhibition in human embryonic stem cells induces a pre-neuroepithelial state that is required for specification to a floor plate cell lineage. Stem Cells 30, 2400-2411.
64. Devine, M. J., Ryten, M., Vodicka, P., Thomson, A. J., Burdon, T., Houlden, H., Cavaleri, F., Nagano, M., Drummond, N. J., Taanman, J.-W. et al. (2011). Parkinson’s disease induced pluripotent stem cells with triplication of the alpha-synuclein locus. Nat. Commun. 2, 440.
65. Di Giovannantonio, L. G., Di Salvio, M., Acampora, D., Prakash, N., Wurst, W. and Simeone, A. (2013). Otx2 selectively controls the neurogenesis of specific neuronal subtypes of the ventral tegmental area and compensates En1-dependent neuronal loss and MPTP vulnerability. Dev. Biol. 373, 176-183.
66. Di Salvio, M., Di Giovannantonio, L. G., Acampora, D., Prosperi, R., Omodei, D., Prakash, N., Wurst, W. and Simeone, A. (2010a). Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP. Nat. Neurosci. 13, 1481-1488.
67. Di Salvio, M., Di Giovannantonio, L. G., Omodei, D., Acampora, D. and Simeone, A. (2010b). Otx2 expression is restricted to dopaminergic neurons of the ventral tegmental area in the adult brain. Int. J. Dev. Biol. 54, 939-945.
68. Doi, D., Samata, B., Katsukawa, M., Kikuchi, T., Morizane, A., Ono, Y., Sekiguchi, K., Nakagawa, M., Parmar, M. and Takahashi, J. (2014). Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation. Stem Cell Rep. 2, 337-350.
69. Ellisor, D., Rieser, C., Voelcker, B., Machan, J. T. and Zervas, M. (2012). Genetic dissection of midbrain dopamine neuron development in vivo. Dev. Biol. 372, 249-262.
70. Ericson, J., Morton, S., Kawakami, A., Roelink, H. and Jessell, T. M. (1996). Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Cell 87, 661-673.
71. Evans, J. R., Mason, S. L. and Barker, R. A. (2012). Current status of clinical trials of neural transplantation in Parkinson’s disease. Prog. Brain Res. 200, 169-198.
72. Falk, A., Koch, P., Kesavan, J., Takashima, Y., Ladewig, J., Alexander, M., Wiskow, O., Tailor, J., Trotter, M., Pollard, S. et al. (2012). Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons. PLoS ONE 7, e29597.
73. Fasano, C. A., Chambers, S. M., Lee, G., Tomishima, M. J. and Studer, L. (2010). Efficient derivation of functional floor plate tissue from human embryonic stem cells. Cell Stem Cell 6, 336-347.
74. Ferri, A. L. M., Lin, W., Mavromatakis, Y. E., Wang, J. C., Sasaki, H., Whitsett, J. A. and Ang, S.-L. (2007). Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. Development 134, 2761-2769.
75. Flores, C., Manitt, C., Rodaros, D., Thompson, K. M., Rajabi, H., Luk, K. C., Tritsch, N. X., Sadikot, A. F., Stewart, J. and Kennedy, T. E. (2005). Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine. Mol. Psychiatry 10, 606-612.
76. Foix, C. and Nicolesco, J. (1925). Anatomie ceŕébrale; les noyaux gris centraux et la reǵion meśenceṕhalo-sous-optique. Paris: Masson et cie.
77. Fox, S. H., Brotchie, J. M. and Lang, A. E. (2008). Non-dopaminergic treatments in development for Parkinson’s disease. Lancet Neurol. 7, 927-938.
78. Freeman, T. B., Spence, M. S., Boss, B. D., Spector, D. H., Strecker, R. E., Olanow, C. W. and Kordower, J. H. (1991). Development of dopaminergic neurons in the human substantia nigra. Exp. Neurol. 113, 344-353.
79. Friling, S., Andersson, E., Thompson, L. H., Jonsson, M. E., Hebsgaard, J. B., Nanou, E., Alekseenko, Z., Marklund, U., Kjellander, S., Volakakis, N. et al. (2009). Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells. Proc. Natl. Acad. Sci. USA 106, 7613-7618.
80. Frim, D. M., Uhler, T. A., Galpern, W. R., Beal, M. F., Breakefield, X. O. and Isacson, O. (1994). Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc. Natl. Acad. Sci. USA 91, 5104-5108.
81. Ganat, Y. M., Calder, E. L., Kriks, S., Nelander, J., Tu, E. Y., Jia, F., Battista, D., Harrison, N., Parmar, M., Tomishima, M. J. et al. (2012). Identification of embryonic stem cell-derived midbrain dopaminergic neurons for engraftment. J. Clin. Invest. 122, 2928-2939.
82. Gash, D. M., Zhang, Z., Ovadia, A., Cass, W. A., Yi, A., Simmerman, L., Russell, D., Martin, D., Lapchak, P. A., Collins, F. et al. (1996). Functional recovery in parkinsonian monkeys treated with GDNF. Nature 380, 252-255.
83. Gil, M., McKinney, C., Lee, M. K., Eells, J. B., Phyillaier, M. A. and Nikodem, V. M. (2007). Regulation of GTP cyclohydrolase I expression by orphan receptor Nurr1 in cell culture and in vivo. J. Neurochem. 101, 142-150.
84. Graham, D. G. (1979). On the origin and significance of neuromelanin. Arch. Pathol. Lab. Med. 103, 359-362.
85. Grande, A., Sumiyoshi, K., Loṕez-Juaŕez, A., Howard, J., Sakthivel, B., Aronow, B., Campbell, K. and Nakafuku, M. (2013). Environmental impact on direct neuronal reprogramming in vivo in the adult brain. Nat. Commun. 4, 2373.
86. Grealish, S., Jonsson, M. E., Li, M., Kirik, D., Bjorklund, A. and Thompson, L. H. (2010). The A9 dopamine neuron component in grafts of ventral mesencephalon is an important determinant for recovery of motor function in a rat model of Parkinson’s disease. Brain 133, 482-495.
87. Grealish, S., Diguet, E., Kirkeby, A., Mattsson, B., Heuer, A., Bramoulle, Y., Van Camp, N., Perrier, A. L., Hantraye, P., Björklund, A. et al. (2014). Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson’s disease. Cell Stem Cell 15, 653-665.
88. Guo, Z., Zhang, L., Wu, Z., Chen, Y., Wang, F. and Chen, G. (2014). In Vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model. Cell Stem Cell 14, 188-202.
89. Hallett, P. J., Cooper, O., Sadi, D., Robertson, H., Mendez, I. and Isacson, O. (2014). Long-term health of dopaminergic neuron transplants in Parkinson’s disease patients. Cell Rep. 7, 1755-1761.
90. Halliday, G., Lees, A. and Stern, M. (2011). Milestones in Parkinson’s disease– clinical and pathologic features. Mov. Disord. 26, 1015-1021.
91. Hanaway, J., McConnell, J. A. and Netsky, M. G. (1971). Histogenesis of the substantia nigra, ventral tegmental area of Tsai and interpeduncular nucleus: an autoradiographic study of the mesencephalon in the rat. J. Comp. Neurol. 142, 59-73.
92. Hargus, G., Cooper, O., Deleidi, M., Levy, A., Lee, K., Marlow, E., Yow, A., Soldner, F., Hockemeyer, D., Hallett, P. J. et al. (2010). Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc. Natl. Acad. Sci. USA 107, 15921-15926.
93. Hassler, R. (1938). Zur Pathologie der Paralysis agitains und des postenzephalitischen Parkinsonismus. J. Psychiatr. Neurol. 48, 387-476.
94. Hayes, L., Zhang, Z., Albert, P., Zervas, M. and Ahn, S. (2011). Timing of Sonic hedgehog and Gli1 expression segregates midbrain dopamine neurons. J. Comp. Neurol. 519, 3001-3018.
95. Heinrich, C., Blum, R., Gascoń, S., Masserdotti, G., Tripathi, P., Sańchez, R., Tiedt, S., Schroeder, T., Götz, M. and Berninger, B. (2010). Directing astroglia from the cerebral cortex into subtype specific functional neurons. PLoS Biol. 8, e1000373.
96. Heinrich, C., Gascoń, S., Masserdotti, G., Lepier, A., Sanchez, R., Simon-Ebert, T., Schroeder, T., Götz, M. and Berninger, B. (2011). Generation of subtype-specific neurons from postnatal astroglia of the mouse cerebral cortex. Nat. Protoc. 6, 214-228.
97. Heinrich, C., Bergami, M., Gascoń, S., Lepier, A., Viganò, F., Dimou, L., Sutor, B., Berninger, B. and Götz, M. (2014). Sox2-mediated conversion of NG2 Glia into induced neurons in the injured adult cerebral cortex. Stem Cell Rep. 3, 1000-1014.
98. Heins, N., Malatesta, P., Cecconi, F., Nakafuku, M., Tucker, K. L., Hack, M. A., Chapouton, P., Barde, Y.-A. and Götz, M. (2002). Glial cells generate neurons: the role of the transcription factor Pax6. Nat. Neurosci. 5, 308-315.
99. Hockemeyer, D., Soldner, F., Beard, C., Gao, Q., Mitalipova, M., DeKelver, R. C., Katibah, G. E., Amora, R., Boydston, E. A., Zeitler, B. et al. (2009). Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat. Biotechnol. 27, 851-857.
100. Horger, B. A., Nishimura, M. C., Armanini, M. P., Wang, L. C., Poulsen, K. T., Rosenblad, C., Kirik, D., Moffat, B., Simmons, L., Johnson, E. Jr. et al. (1998). Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J. Neurosci. 18, 4929-4937.
101. Hornykiewicz, O. (1978). Psychopharmacological implications of dopamine and dopamine antagonists: a critical evaluation of current evidence. Neuroscience 3, 773-783.
102. Horowski, R., Horowski, L., Phil, C., Vogel, S., Poewe, W. and Kielhorn, F.-W. (1995). An essay on Wilhelm Von Humboldt and the shaking palsy: first comprehensive description of Parkinson’s disease by a patient. Neurology 45, 565-568.
103. Hur, E.-M. and Zhou, F.-Q. (2010). GSK3 signalling in neural development. Nat. Rev. Neurosci. 11, 539-551.
104. Hwang, D.-Y., Ardayfio, P., Kang, U. J., Semina, E. V. and Kim, K.-S. (2003). Selective loss of dopaminergic neurons in the substantia nigra of Pitx3-deficient aphakia mice. Brain Res. Mol. Brain Res. 114, 123-131.
105. Hyman, C., Hofer, M., Barde, Y.-A., Juhasz, M., Yancopoulos, G. D., Squinto, S. P. and Lindsay, R. M. (1991). BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350, 230-232.
106. Jacobs, F. M. J., Smits, S. M., Noorlander, C. W., von Oerthel, L., van der Linden, A. J. A., Burbach, J. P. H. and Smidt, M. P. (2007). Retinoic acid counteracts developmental defects in the substantia nigra caused by Pitx3 deficiency. Development 134, 2673-2684.
107. Jacobs, F. M. J., van Erp, S., van der Linden, A. J. A., von Oerthel, L., Burbach, J. P. H. and Smidt, M. P. (2009). Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression. Development 136, 531-540.
108. Jacobs, F. M. J., Veenvliet, J. V., Almirza, W. H., Hoekstra, E. J., von Oerthel, L., van der Linden, A. J. A., Neijts, R., Koerkamp, M. G., van Leenen, D., Holstege, F. C. P. et al. (2011). Retinoic acid-dependent and -independent gene-regulatory pathways of Pitx3 in meso-diencephalic dopaminergic neurons. Development 138, 5213-5222.
109. Jaeger, I., Arber, C., Risner-Janiczek, J. R., Kuechler, J., Pritzsche, D., Chen, I.-C., Naveenan, T., Ungless, M. A. and Li, M. (2011). Temporally controlled modulation of FGF/ERK signaling directs midbrain dopaminergic neural progenitor fate in mouse and human pluripotent stem cells. Development 138, 4363-4374.
110. Jain, S. and Heutink, P. (2010). From single genes to gene networks: high-throughput-high-content screening for neurological disease. Neuron 68, 207-217.
111. Jankovic, J. and Aguilar, L. G. (2008). Current approaches to the treatment of Parkinson’s disease. Neuropsychiatr. Dis. Treatment 4, 743-757.
112. Jankovic, J. and Poewe, W. (2012). Therapies in Parkinson’s disease. Curr. Opin. Neurol. 25, 433-447.
113. Jankovic, J., Chen, S. and Le, W. D. (2005). The role of Nurr1 in the development of dopaminergic neurons and Parkinson’s disease. Prog. Neurobiol. 77, 128-138.
114. Jellinger, K. A. (1991). Pathology of Parkinson’s disease. Changes other than the nigrostriatal pathway. Mol. Chem. Neuropathol. 14, 153-197.
115. Joksimovic, M., Anderegg, A., Roy, A., Campochiaro, L., Yun, B., Kittappa, R., McKay, R. and Awatramani, R. (2009a). Spatiotemporally separable Shh domains in the midbrain define distinct dopaminergic progenitor pools. Proc. Natl. Acad. Sci. USA 106, 19185-19190.
116. Joksimovic, M., Yun, B. A., Kittappa, R., Anderegg, A. M., Chang, W. W., Taketo, M. M., McKay, R. D. G. and Awatramani, R. B. (2009b). Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis. Nat. Neurosci. 12, 125-131.
117. Jönsson, M. E., Ono, Y., Björklund, A. and Thompson, L. H. (2009). Identification of transplantable dopamine neuron precursors at different stages of midbrain neurogenesis. Exp. Neurol. 219, 341-354.
118. Joseph, B., Wallen-Mackenzie, A., Benoit, G., Murata, T., Joodmardi, E., Okret, S. and Perlmann, T. (2003). p57(Kip2) cooperates with Nurr1 in developing dopamine cells. Proc. Natl. Acad. Sci. USA 100, 15619-15624.
119. Joyner, A. L., Liu, A. and Millet, S. (2000). Otx2, Gbx2 and Fgf8 interact to position and maintain a mid-hindbrain organizer. Curr. Opin. Cell Biol. 12, 736-741.
120. Kadkhodaei, B., Ito, T., Joodmardi, E., Mattsson, B., Rouillard, C., Carta, M., Muramatsu, S.-I., Sumi-Ichinose, C., Nomura, T., Metzger, D. et al. (2009). Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. J. Neurosci. 29, 15923-15932.
121. Kadoshima, T., Sakaguchi, H., Nakano, T., Soen, M., Ando, S., Eiraku, M. and Sasai, Y. (2013). Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc. Natl. Acad. Sci. USA 110, 20284-20289.
122. Kang, W.-Y., Kim, S.-S., Cho, S.-K., Kim, S., Suh-Kim, H. and Lee, Y.-D. (2010). Migratory defect of mesencephalic dopaminergic neurons in developing reeler mice. Anat. Cell Biol. 43, 241-251.
123. Karow, M., Sańchez, R., Schichor, C., Masserdotti, G., Ortega, F., Heinrich, C., Gascon, S., Khan, M. A., Lie, D. C., Dellavalle, A. et al. (2012). Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells. Cell Stem Cell 11, 471-476.
124. Kawano, H., Ohyama, K., Kawamura, K. and Nagatsu, I. (1995). Migration of dopaminergic neurons in the embryonic mesencephalon of mice. Brain Res. Dev. Brain Res. 86, 101-113.
125. Kawasaki, H., Mizuseki, K., Nishikawa, S., Kaneko, S., Kuwana, Y., Nakanishi, S., Nishikawa, S.-I. and Sasai, Y. (2000). Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28, 31-40.
126. Kele, J., Simplicio, N., Ferri, A. L. M., Mira, H., Guillemot, F., Arenas, E. and Ang, S.-L. (2006). Neurogenin 2 is required for the development of ventral midbrain dopaminergic neurons. Development 133, 495-505.
127. Kim, J.-H., Auerbach, J. M., Rodrıǵuez-Goḿez, J. A., Velasco, I., Gavin, D., Lumelsky, N., Lee, S.-H., Nguyen, J., Sańchez-Pernaute, R., Bankiewicz, K. et al. (2002). Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418, 50-56.
128. Kim, J., Su, S. C., Wang, H., Cheng, A. W., Cassady, J. P., Lodato, M. A., Lengner, C. J., Chung, C.-Y., Dawlaty, M. M., Tsai, L.-H. et al. (2011). Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell 9, 413-419.
129. Kirkeby, A., Grealish, S., Wolf, D. A., Nelander, J., Wood, J., Lundblad, M., Lindvall, O. and Parmar, M. (2012). Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions. Cell Rep. 1, 703-714.
130. Kiskinis, E. and Eggan, K. (2010). Progress toward the clinical application of patient-specific pluripotent stem cells. J. Clin. Invest. 120, 51-59.
131. Koch, P., Opitz, T., Steinbeck, J. A., Ladewig, J. and Brustle, O. (2009). A rosette-type, self-renewing human ES cell-derived neural stem cell with potential for in vitro instruction and synaptic integration. Proc. Natl. Acad. Sci. USA 106, 3225-3230.
132. Kordower, J. H., Emborg, M. E., Bloch, J., Ma, S. Y., Chu, Y., Leventhal, L., McBride, J., Chen, E.-Y., Palfi, S., Roitberg, B. Z. et al. (2000). Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 290, 767-773.
133. Krieglstein, K., Farkas, L. and Unsicker, K. (1998). TGF-beta regulates the survival of ciliary ganglionic neurons synergistically with ciliary neurotrophic factor and neurotrophins. J. Neurobiol. 37, 563-572.
134. Kriks, S., Shim, J.-W., Piao, J., Ganat, Y. M., Wakeman, D. R., Xie, Z., Carrillo Reid, L., Auyeung, G., Antonacci, C., Buch, A. et al. (2011). Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480, 547-551.
135. Ladewig, J., Mertens, J., Kesavan, J., Doerr, J., Poppe, D., Glaue, F., Herms, S., Wernet, P., Kögler, G., Müller, F.-J. et al. (2012). Small molecules enable highly efficient neuronal conversion of human fibroblasts. Nat. Methods 9, 575-578.
136. Ladewig, J., Koch, P. and Brüstle, O. (2013). Leveling Waddington: the emergence of direct programming and the loss of cell fate hierarchies. Nat. Rev. Mol. Cell Biol. 14, 225-236.
137. Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P. and Knoblich, J. A. (2013). Cerebral organoids model human brain development and microcephaly. Nature 501, 373-379.
138. Le, W.-d., Conneely, O. M., Zou, L., He, Y., Saucedo-Cardenas, O., Jankovic, J., Mosier, D. R. and Appel, S. H. (1999). Selective agenesis of mesencephalic dopaminergic neurons in Nurr1-deficient mice. Exp. Neurol. 159, 451-458.
139. Lee, S.-H., Lumelsky, N., Studer, L., Auerbach, J. M. and McKay, R. D. (2000). Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat. Biotechnol. 18, 675-679.
140. Lees, A. J., Hardy, J. and Revesz, T. (2009). Parkinson’s disease. Lancet 373, 2055-2066.
141. Lin, L. F., Doherty, D. H., Lile, J. D., Bektesh, S. and Collins, F. (1993). GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260, 1130-1132.
142. Lin, W., Metzakopian, E., Mavromatakis, Y. E., Gao, N., Balaskas, N., Sasaki, H., Briscoe, J., Whitsett, J. A., Goulding, M., Kaestner, K. H. et al. (2009). Foxa1 and Foxa2 function both upstream of and cooperatively with Lmx1a and Lmx1b in a feedforward loop promoting mesodiencephalic dopaminergic neuron development. Dev. Biol. 333, 386-396.
143. Lindholm, P., Voutilainen, M. H., Laureń, J., Peränen, J., Leppänen, V.-M., Andressoo, J.-O., Lindahl, M., Janhunen, S., Kalkkinen, N., Timmusk, T. et al. (2007). Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo. Nature 448, 73-77.
144. Lindvall, O. and Björklund, A. (2004). Cell therapy in Parkinson’s disease. NeuroRx 1, 382-393.
145. Lindvall, O. and Björklund, A. (2011). Cell therapeutics in Parkinson’s disease. Neurotherapeutics 8, 539-548.
146. Liu, G.-H., Qu, J., Suzuki, K., Nivet, E., Li, M., Montserrat, N., Yi, F., Xu, X., Ruiz, S., Zhang, W. et al. (2012a). Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature 491, 603-607.
147. Liu, X., Li, F., Stubblefield, E. A., Blanchard, B., Richards, T. L., Larson, G. A., He, Y., Huang, Q., Tan, A.-C., Zhang, D. et al. (2012b). Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Res. 22, 321-332.
148. Livesey, F. J. and Hunt, S. P. (1997). Netrin and netrin receptor expression in the embryonic mammalian nervous system suggests roles in retinal, striatal, nigral, and cerebellar development. Mol. Cell. Neurosci. 8, 417-429.
149. Lloyd, K. and Hornykiewicz, O. (1970). Parkinson’s disease: activity of L-dopa decarboxylase in discrete brain regions. Science 170, 1212-1213.
150. Maciaczyk, J., Singec, I., Maciaczyk, D. and Nikkhah, G. (2008). Combined use of BDNF, ascorbic acid, low oxygen, and prolonged differentiation time generates tyrosine hydroxylase-expressing neurons after long-term in vitro expansion of human fetal midbrain precursor cells. Exp. Neurol. 213, 354-362.
151. Maetzel, D., Sarkar, S., Wang, H., Abi-Mosleh, L., Xu, P., Cheng, A. W., Gao, Q., Mitalipova, M. and Jaenisch, R. (2014). Genetic and chemical correction of cholesterol accumulation and impaired autophagy in hepatic and neural cells derived from Niemann-Pick Type C patient-specific iPS cells. Stem Cell Rep. 2, 866-880.
152. Marchand, R. and Poirier, L. J. (1983). Isthmic origin of neurons of the rat substantia nigra. Neuroscience 9, 373-381.
153. Marro, S., Pang, Z. P., Yang, N., Tsai, M.-C., Qu, K., Chang, H. Y., Südhof, T. C. and Wernig, M. (2011). Direct lineage conversion of terminally differentiated hepatocytes to functional neurons. Cell Stem Cell 9, 374-382.
154. Marti, E., Bumcrot, D. A., Takada, R. and McMahon, A. P. (1995). Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Nature 375, 322-325.
155. Martinez, S., Crossley, P. H., Cobos, I., Rubenstein, J. L. and Martin, G. R. (1999). FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression. Development 126, 1189-1200.
156. Maxwell, S. L., Ho, H.-Y., Kuehner, E., Zhao, S. and Li, M. (2005). Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development. Dev. Biol. 282, 467-479.
157. Mazzulli, J. R., Xu, Y.-H., Sun, Y., Knight, A. L., McLean, P. J., Caldwell, G. A., Sidransky, E., Grabowski, G. A. and Krainc, D. (2011). Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 146, 37-52.
158. McMahon, A. P. and Bradley, A. (1990). The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell 62, 1073-1085.
159. McMahon, A. P., Joyner, A. L., Bradley, A. and McMahon, J. A. (1992). The midbrain-hindbrain phenotype of Wnt-1-/Wnt-1- mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum. Cell 69, 581-595.
160. Metzakopian, E., Lin, W., Salmon-Divon, M., Dvinge, H., Andersson, E., Ericson, J., Perlmann, T., Whitsett, J. A., Bertone, P. and Ang, S.-L. (2012). Genome-wide characterization of Foxa2 targets reveals upregulation of floor plate genes and repression of ventrolateral genes in midbrain dopaminergic progenitors. Development 139, 2625-2634.
161. Millet, S., Campbell, K., Epstein, D. J., Losos, K., Harris, E. and Joyner, A. L. (1999). A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer. Nature 401, 161-164.
162. Millonig, J. H., Millen, K. J. and Hatten, M. E. (2000). The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS. Nature 403, 764-769.
163. Moore, M. W., Klein, R. D., Fariñas, I., Sauer, H., Armanini, M., Phillips, H., Reichardt, L. F., Ryan, A. M., Carver-Moore, K. and Rosenthal, A. (1996). Renal and neuronal abnormalities in mice lacking GDNF. Nature 382, 76-79.
164. Nakatani, T., Kumai, M., Mizuhara, E., Minaki, Y. and Ono, Y. (2010). Lmx1a and Lmx1b cooperate with Foxa2 to coordinate the specification of dopaminergic neurons and control of floor plate cell differentiation in the developing mesencephalon. Dev. Biol. 339, 101-113.
165. Nelander, J., Hebsgaard, J. B. and Parmar, M. (2009). Organization of the human embryonic ventral mesencephalon. Gene Expr. Patterns 9, 555-561.
166. Nguyen, H. N., Byers, B., Cord, B., Shcheglovitov, A., Byrne, J., Gujar, P., Kee, K., Schüle, B., Dolmetsch, R. E., Langston, W. et al. (2011). LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8, 267-280.
167. Nishikawa, S., Goto, S., Yamada, K., Hamasaki, T. and Ushio, Y. (2003). Lack of Reelin causes malpositioning of nigral dopaminergic neurons: evidence from comparison of normal and Reln(rl) mutant mice. J. Comp. Neurol. 461, 166-173.
168. Niu, W., Zang, T., Zou, Y., Fang, S., Smith, D. K., Bachoo, R. and Zhang, C.-L. (2013). In vivo reprogramming of astrocytes to neuroblasts in the adult brain. Nat. Cell Biol. 15, 1164-1175.
169. Nunes I.,Tovmasian, L.T., Silva, R.M., Burke, R.E. and Goff, S.P. (2003). Pitx3 is required for development of substantia nigra dopaminergic neurons. Proc. Natl. Acad. Sci. USA 100, 4245-4250.
170. Ohyama, K., Kawano, H., Asou, H., Fukuda, T., Oohira, A., Uyemura, K. and Kawamura, K. (1998). Coordinate expression of L1 and 6B4 proteoglycan/ phosphacan is correlated with the migration of mesencephalic dopaminergic neurons in mice. Brain Res. Dev. Brain Res. 107, 219-226.
171. Omodei, D., Acampora, D., Mancuso, P., Prakash, N., Di Giovannantonio, L. G., Wurst, W. and Simeone, A. (2008). Anterior-posterior graded response to Otx2 controls proliferation and differentiation of dopaminergic progenitors in the ventral mesencephalon. Development 135, 3459-3470.
172. Ono, Y., Nakatani, T., Sakamoto, Y., Mizuhara, E., Minaki, Y., Kumai, M., Hamaguchi, A., Nishimura, M., Inoue, Y., Hayashi, H. et al. (2007). Differences in neurogenic potential in floor plate cells along an anteroposterior location: midbrain dopaminergic neurons originate from mesencephalic floor plate cells. Development 134, 3213-3225.
173. Ono, Y., Nakatani, T., Minaki, Y. and Kumai, M. (2010). The basic helix-loop-helix transcription factor Nato3 controls neurogenic activity in mesencephalic floor plate cells. Development 137, 1897-1906.
174. Pang, Z. P., Yang, N., Vierbuchen, T., Ostermeier, A., Fuentes, D. R., Yang, T. Q., Citri, A., Sebastiano, V., Marro, S., Südhof, T. C. et al. (2011). Induction of human neuronal cells by defined transcription factors. Nature 476, 220-223.
175. Panman, L., Papathanou, M., Laguna, A., Oosterveen, T., Volakakis, N., Acampora, D., Kurtsdotter, I., Yoshitake, T., Kehr, J., Joodmardi, E. et al. (2014). Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons. Cell Rep. 8, 1018-1025.
176. Parish, C. L., Castelo-Branco, G., Rawal, N., Tonnesen, J., Sorensen, A. T., Salto, C., Kokaia, M., Lindvall, O. and Arenas, E. (2008). Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice. J. Clin. Invest. 118, 149-160.
177. Park, C.-H., Minn, Y.-K., Lee, J.-Y., Choi, D. H., Chang, M.-Y., Shim, J.-W., Ko, J.-Y., Koh, H.-C., Kang, M. J., Kang, J. S. et al. (2005). In vitro and in vivo analyses of human embryonic stem cell-derived dopamine neurons. J. Neurochem. 92, 1265-1276.
178. Pascual, A., Hidalgo-Figueroa, M., Piruat, J. I., Pintado, C. O., Goḿez-Dıáz, R. and Loṕez-Barneo, J. (2008). Absolute requirement of GDNF for adult catecholaminergic neuron survival. Nat. Neurosci. 11, 755-761.
179. Peng, C., Aron, L., Klein, R., Li, M., Wurst, W., Prakash, N. and Le, W. (2011). Pitx3 is a critical mediator of GDNF-induced BDNF expression in nigrostriatal dopaminergic neurons. J. Neurosci. 31, 12802-12815.
180. Perrier, A. L., Tabar, V., Barberi, T., Rubio, M. E., Bruses, J., Topf, N., Harrison, N. L. and Studer, L. (2004). Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc. Natl. Acad. Sci. USA 101, 12543-12548.
181. Petrova, P. S., Raibekas, A., Pevsner, J., Vigo, N., Anafi, M., Moore, M. K., Peaire, A. E., Shridhar, V., Smith, D. I., Kelly, J. et al. (2003). MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons. J. Mol. Neurosci. 20, 173-188.
182. Pfisterer, U., Kirkeby, A., Torper, O., Wood, J., Nelander, J., Dufour, A., Bjorklund, A., Lindvall, O., Jakobsson, J. and Parmar, M. (2011). Direct conversion of human fibroblasts to dopaminergic neurons. Proc. Natl. Acad. Sci. USA 108, 10343-10348.
183. Pichel, J. G., Shen, L., Sheng, H. Z., Granholm, A.-C., Drago, J., Grinberg, A., Lee, E. J., Huang, S. P., Saarma, M., Hoffer, B. J. et al. (1996). Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382, 73-76.
184. Placzek, M. and Briscoe, J. (2005). The floor plate: multiple cells, multiple signals. Nat. Rev. Neurosci. 6, 230-240.
185. Politis, M., Wu, K., Loane, C., Quinn, N. P., Brooks, D. J., Rehncrona, S., Bjorklund, A., Lindvall, O. and Piccini, P. (2010). Serotonergic neurons mediate dyskinesia side effects in Parkinson’s patients with neural transplants. Sci. Transl. Med. 2, 38ra46.
186. Poulin, J.-F., Zou, J., Drouin-Ouellet, J., Kim, K.-Y. A., Cicchetti, F. and Awatramani, R. B. (2014). Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling. Cell Rep. 9, 930-943.
187. Poulsen, K. T., Armanini, M. P., Klein, R. D., Hynes, M. A., Phillips, H. S. and Rosenthal, A. (1994). TGF beta 2 and TGF beta 3 are potent survival factors for midbrain dopaminergic neurons. Neuron 13, 1245-1252.
188. Prakash, N., Brodski, C., Naserke, T., Puelles, E., Gogoi, R., Hall, A., Panhuysen, M., Echevarria, D., Sussel, L., Weisenhorn, D. M. V. et al. (2006). A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo. Development 133, 89-98.
189. Pruszak, J., Sonntag, K.-C., Aung, M. H., Sanchez-Pernaute, R. and Isacson, O. (2007). Markers and methods for cell sorting of human embryonic stem cell-derived neural cell populations. Stem Cells 25, 2257-2268.
190. Puelles, E., Annino, A., Tuorto, F., Usiello, A., Acampora, D., Czerny, T., Brodski, C., Ang, S.-L., Wurst, W. and Simeone, A. (2004). Otx2 regulates the extent, identity and fate of neuronal progenitor domains in the ventral midbrain. Development 131, 2037-2048.
191. Qiang, L., Fujita, R., Yamashita, T., Angulo, S., Rhinn, H., Rhee, D., Doege, C., Chau, L., Aubry, L., Vanti, W. B. et al. (2011). Directed conversion of Alzheimer’s disease patient skin fibroblasts into functional neurons. Cell 146, 359-371.
192. Ramos-Moreno, T., Castillo, C. G. and Martıńez-Serrano, A. (2012). Long term behavioral effects of functional dopaminergic neurons generated from human neural stem cells in the rat 6-OH-DA Parkinson’s disease model. Effects of the forced expression of BCL-X(L). Behav. Brain Res. 232, 225-232.
193. Reinhardt, P., Schmid, B., Burbulla, L. F., Schöndorf, D. C., Wagner, L., Glatza, M., Höing, S., Hargus, G., Heck, S. A., Dhingra, A. et al. (2013). Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression. Cell Stem Cell 12, 354-367.
194. Rhinn, M., Dierich, A., Shawlot, W., Behringer, R. R., Le Meur, M. and Ang, S. L. (1998). Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification. Development 125, 845-856.
195. Rhinn, M., Dierich, A., Le Meur, M. and Ang, S. (1999). Cell autonomous and non-cell autonomous functions of Otx2 in patterning the rostral brain. Development 126, 4295-4304.
196. Riaz, S. S., Jauniaux, E., Stern, G. M. and Bradford, H. F. (2002). The controlled conversion of human neural progenitor cells derived from foetal ventral mesencephalon into dopaminergic neurons in vitro. Brain Res. Dev. Brain Res. 136, 27-34.
197. Ribeiro, D., Laguna Goya, R., Ravindran, G., Vuono, R., Parish, C. L., Foldi, C., Piroth, T., Yang, S., Parmar, M., Nikkhah, G. et al. (2012). Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens. Neurobiol. Dis. 49C, 118-127.
198. Riedl, S. J. and Salvesen, G. S. (2007). The apoptosome: signalling platform of cell death. Nat. Rev. Mol. Cell Biol. 8, 405-413.
199. Roelink, H., Porter, J. A., Chiang, C., Tanabe, Y., Chang, D. T., Beachy, P. A. and Jessell, T. M. (1995). Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell 81, 445-455.
200. Roeper, J. (2013). Dissecting the diversity of midbrain dopamine neurons. Trends Neurosci. 36, 336-342.
201. Rosenblad, C., Martinez-Serrano, A. and Björklund, A. (1998). Intrastriatal glial cell line-derived neurotrophic factor promotes sprouting of spared nigrostriatal dopaminergic afferents and induces recovery of function in a rat model of Parkinson’s disease. Neuroscience 82, 129-137.
202. Rosenblad, C., Kirik, D., Devaux, B., Moffat, B., Phillips, H. S. and Bjorklund, A. (1999). Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson’s disease after administration into the striatum or the lateral ventricle. Eur. J. Neurosci. 11, 1554-1566.
203. Rosenblad, C., Gronborg, M., Hansen, C., Blom, N., Meyer, M., Johansen, J., Dago, L., Kirik, D., Patel, U. A., Lundberg, C. et al. (2000). In vivo protection of nigral dopamine neurons by lentiviral gene transfer of the novel GDNF-family member neublastin/artemin. Mol. Cell. Neurosci. 15, 199-214.
204. Rouaux, C. and Arlotta, P. (2013). Direct lineage reprogramming of post-mitotic callosal neurons into corticofugal neurons in vivo. Nat. Cell Biol. 15, 214-221.
205. Roussa, E., von Bohlen und Halbach, O. and Krieglstein, K. (2009). TGF-beta in dopamine neuron development, maintenance and neuroprotection. Adv. Exp. Med. Biol. 651, 81-90.
206. Roy, N. S., Cleren, C., Singh, S. K., Yang, L., Beal, M. F. and Goldman, S. A. (2006). Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nat. Med. 12, 1259-1268.
207. Ryan, S. D., Dolatabadi, N., Chan, S. F., Zhang, X., Akhtar, M. W., Parker, J., Soldner, F., Sunico, C. R., Nagar, S., Talantova, M. et al. (2013). Isogenic human iPSC Parkinson’s model shows nitrosative stress-induced dysfunction in MEF2-PGC1alpha transcription. Cell 155, 1351-1364.
208. Sacchetti, P., Sousa, K. M., Hall, A. C., Liste, I., Steffensen, K. R., Theofilopoulos, S., Parish, C. L., Hazenberg, C., Richter, L. A., Hovatta, O. et al. (2009). Liver X receptors and oxysterols promote ventral midbrain neurogenesis in vivo and in human embryonic stem cells. Cell Stem Cell 5, 409-419.
209. Sanchez, M. P., Silos-Santiago, I., Friseń, J., He, B., Lira, S. A. and Barbacid, M. (1996). Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382, 70-73.
210. Sanchez-Danes, A., Consiglio, A., Richaud, Y., Rodriguez-Piza, I., Dehay, B., Edel, M., Bove, J., Memo, M., Vila, M., Raya, A. et al. (2012a). Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery of LMX1A in human embryonic stem cells and induced pluripotent stem cells. Hum. Gene Ther. 23, 56-69.
211. Sanchez-Danes, A., Richaud-Patin, Y., Carballo-Carbajal, I., Jimenez-Delgado, S., Caig, C., Mora, S., Di Guglielmo, C., Ezquerra, M., Patel, B., Giralt, A. et al. (2012b). Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Mol. Med. 4, 380-395.
212. Sanchez-Pernaute, R., Studer, L., Bankiewicz, K. S., Major, E. O. and McKay, R. D. G. (2001). In vitro generation and transplantation of precursor-derived human dopamine neurons. J. Neurosci. Res. 65, 284-288.
213. Sanders, L. H., Laganière, J., Cooper, O., Mak, S. K., Vu, B. J., Huang, Y. A., Paschon, D. E., Vangipuram, M., Sundararajan, R., Urnov, F. D. et al. (2014). LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson’s disease patients: reversal by gene correction. Neurobiol. Dis. 62, 381-386.
214. Sasaki, H., Hui, C., Nakafuku, M. and Kondoh, H. (1997). A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh in vitro. Development 124, 1313-1322.
215. Sato, T. and Nakamura, H. (2004). The Fgf8 signal causes cerebellar differentiation by activating the Ras-ERK signaling pathway. Development 131, 4275-4285.
216. Saucedo-Cardenas, O., Quintana-Hau, J. D., Le, W.-D., Smidt, M. P., Cox, J. J., De Mayo, F., Burbach, J. P. H. and Conneely, O. M. (1998). Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc. Natl. Acad. Sci. USA 95, 4013-4018.
217. Schöndorf, D. C., Aureli, M., McAllister, F. E., Hindley, C. J., Mayer, F., Schmid, B., Sardi, S. P., Valsecchi, M., Hoffmann, S., Schwarz, L. K. et al. (2014). iPSC-derived neurons from GBA1-associated Parkinson’s disease patients show autophagic defects and impaired calcium homeostasis. Nat. Commun. 5, 4028.
218. Seibler, P., Graziotto, J., Jeong, H., Simunovic, F., Klein, C. and Krainc, D. (2011). Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells. J. Neurosci. 31, 5970-5976.
219. Semina, E. V., Reiter, R. S. and Murray, J. C. (1997). Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19. Hum. Mol. Genet. 6, 2109-2116.
220. Sharaf, A., Bock, H. H., Spittau, B., Bouché, E. and Krieglstein, K. (2013). ApoER2 and VLDLr are required for mediating reelin signalling pathway for normal migration and positioning of mesencephalic dopaminergic neurons. PLoS ONE 8, e71091.
221. Shimamura, K., Hirano, S., McMahon, A. P. and Takeichi, M. (1994). Wnt-1-dependent regulation of local E-cadherin and alpha N-catenin expression in the embryonic mouse brain. Development 120, 2225-2234.
222. Shults, C. W., Hashimoto, R., Brady, R. M. and Gage, F. H. (1990). Dopaminergic cells align along radial glia in the developing mesencephalon of the rat. Neuroscience 38, 427-436.
223. Smidt, M. P. and Burbach, J. P. H. (2007). How to make a mesodiencephalic dopaminergic neuron. Nat. Rev. Neurosci. 8, 21-32.
224. Smidt, M. P., van Schaick, H. S. A., Lanctot, C., Tremblay, J. J., Cox, J. J., van der Kleij, A. A. M., Wolterink, G., Drouin, J. and Burbach, J. P. H. (1997). A homeodomain gene Ptx3 has highly restricted brain expression in mesencephalic dopaminergic neurons. Proc. Natl. Acad. Sci. USA 94, 13305-13310.
225. Smidt, M. P., Asbreuk, C. H. J., Cox, J. J., Chen, H., Johnson, R. L. and Burbach, J. P. (2000). A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nat. Neurosci. 3, 337-341.
226. Smidt, M. P., Smits, S. M., Bouwmeester, H., Hamers, F. P. T., van der Linden, A. J. A., Hellemons, A. J. C. G. M., Graw, J. and Burbach, J. P. H. (2004). Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3. Development 131, 1145-1155.
227. Smits, S. M., Ponnio, T., Conneely, O. M., Burbach, J. P. H. and Smidt, M. P. (2003). Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons. Eur. J. Neurosci. 18, 1731-1738.
228. Soldner, F., Laganière, J., Cheng, A. W., Hockemeyer, D., Gao, Q., Alagappan, R., Khurana, V., Golbe, L. I., Myers, R. H., Lindquist, S. et al. (2011). Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146, 318-331.
229. Sousa, K. M., Mira, H., Hall, A. C., Jansson-Sjöstrand, L., Kusakabe, M. and Arenas, E. (2007). Microarray analyses support a role for Nurr1 in resistance to oxidative stress and neuronal differentiation in neural stem cells. Stem Cells 25, 511-519.
230. Steinbeck, J. A., Choi, S. J., Mrejeru, A., Ganat, Y., Deisseroth, K., Sulzer, D., Mosharov, E. V. and Studer, L. (2015). Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson’s disease model. Nat. Biotechnol. 33, 204-209.
231. Stern, M. B., Marek, K. L., Friedman, J., Hauser, R. A., LeWitt, P. A., Tarsy, D. and Olanow, C. W. (2004). Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson’s disease patients. Mov. Disord. 19, 916-923.
232. Stott, S. R. W., Metzakopian, E., Lin, W., Kaestner, K. H., Hen, R. and Ang, S. L. (2013). Foxa1 and foxa2 are required for the maintenance of dopaminergic properties in ventral midbrain neurons at late embryonic stages. J. Neurosci. 33, 8022-8034.
233. Su, Z., Niu, W., Liu, M.-L., Zou, Y. and Zhang, C.-L. (2014). In vivo conversion of astrocytes to neurons in the injured adult spinal cord. Nat. Commun. 5, 3338.
234. Sundberg, M., Bogetofte, H., Lawson, T., Jansson, J., Smith, G., Astradsson, A., Moore, M., Osborn, T., Cooper, O., Spealman, R. et al. (2013). Improved cell therapy protocols for Parkinson’s disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons. Stem Cells 31, 1548-1562.
235. Suzuki-Hirano, A., Sato, T. and Nakamura, H. (2005). Regulation of isthmic Fgf8 signal by sprouty2. Development 132, 257-265.
236. Tagliavini, F., Pilleri, G., Bouras, C. and Constantinidis, J. (1984). The basal nucleus of Meynert in idiopathic Parkinson’s disease. Acta Neurol. Scand. 70, 20-28.
237. Tailor, J., Kittappa, R., Leto, K., Gates, M., Borel, M., Paulsen, O., Spitzer, S., Karadottir, R. T., Rossi, F., Falk, A. et al. (2013). Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency. J. Neurosci. 33, 12407-12422.
238. Takahashi, K. and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676.
239. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K. and Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872.
240. Takaoka, K., Yamamoto, M. and Hamada, H. (2007). Origin of body axes in the mouse embryo. Curr. Opin. Genet. Dev. 17, 344-350.
241. Tang, M., Miyamoto, Y. and Huang, E. J. (2009). Multiple roles of beta-catenin in controlling the neurogenic niche for midbrain dopamine neurons. Development 136, 2027-2038.
242. Tang, M., Villaescusa, J. C., Luo, S. X., Guitarte, C., Lei, S., Miyamoto, Y., Taketo, M. M., Arenas, E. and Huang, E. J. (2010). Interactions of Wnt/beta-catenin signaling and sonic hedgehog regulate the neurogenesis of ventral midbrain dopamine neurons. J. Neurosci. 30, 9280-9291.
243. Theofilopoulos, S., Wang, Y., Kitambi, S. S., Sacchetti, P., Sousa, K. M., Bodin, K., Kirk, J., Saltó, C., Gustafsson, M., Toledo, E. M. et al. (2013). Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis. Nat. Chem. Biol. 9, 126-133.
244. Thomas, K. R. and Capecchi, M. R. (1990). Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature 346, 847-850.
245. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S. and Jones, J. M. (1998). Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147.
246. Tomac, A., Lindqvist, E., Lin, L.-F. H., Ogren, S. O., Young, D., Hoffer, B. J. and Olson, L. (1995). Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373, 335-339.
247. Torper, O., Pfisterer, U., Wolf, D. A., Pereira, M., Lau, S., Jakobsson, J., Bjorklund, A., Grealish, S. and Parmar, M. (2013). Generation of induced neurons via direct conversion in vivo. Proc. Natl. Acad. Sci. USA 110, 7038-7043.
248. Trupp, M., Arenas, E., Fainzilber, M., Nilsson, A.-S., Sieber, B.-A., Grigoriou, M., Kilkenny, C., Salazar-Grueso, E., Pachnis, V., Arumäe, U. et al. (1996). Functional receptor for GDNF encoded by the c-ret proto-oncogene. Nature 381, 785-789.
249. van den Munckhof, P., Luk, K. C., Ste-Marie, L., Montgomery, J., Blanchet, P. J., Sadikot, A. F. and Drouin, J. (2003). Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons. Development 130, 2535-2542.
250. Veenvliet, J. V., dos Santos, M. T. M. A., Kouwenhoven, W. M., von Oerthel, L., Lim, J. L., van der Linden, A. J. A., Koerkamp, M. J. A. G., Holstege, F. C. P. and Smidt, M. P. (2013). Specification of dopaminergic subsets involves interplay of En1 and Pitx3. Development 140, 3373-3384.
251. Vierbuchen, T., Ostermeier, A., Pang, Z. P., Kokubu, Y., Südhof, T. C. and Wernig, M. (2010). Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463, 1035-1041.
252. Villaescusa, J. C. and Arenas, E. (2010). Transplantable midbrain dopamine neurons: a moving target. Exp. Neurol. 222, 173-178.
253. Volpicelli, F., Caiazzo, M., Greco, D., Consales, C., Leone, L., Perrone-Capano, C., Colucci D’Amato, L. and di Porzio, U. (2007). Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro. J. Neurochem. 102, 441-453.
254. Volpicelli, F., De Gregorio, R., Pulcrano, S., Perrone-Capano, C., di Porzio, U. and Bellenchi, G. C. (2012). Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain. PLoS ONE 7, e30661.
255. Voutilainen, M. H., Back, S., Porsti, E., Toppinen, L., Lindgren, L., Lindholm, P., Peranen, J., Saarma, M. and Tuominen, R. K. (2009). Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson’s disease. J. Neurosci. 29, 9651-9659.
256. Wagner, J., Akerud, P., Castro, D. S., Holm, P. C., Canals, J. M., Snyder, E. Y., Perlmann, T. and Arenas, E. (1999). Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes. Nat. Biotechnol. 17, 653-659.
257. Wallen, A., Castro, D. S., Zetterstrom, R. H., Karlen, M., Olson, L., Ericson, J. and Perlmann, T. (2001). Orphan nuclear receptor Nurr1 is essential for Ret expression in midbrain dopamine neurons and in the brain stem. Mol. Cell. Neurosci. 18, 649-663.
258. Wang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F. and Jaenisch, R. (2013). One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910-918.
259. Wapinski, O. L., Vierbuchen, T., Qu, K., Lee, Q. Y., Chanda, S., Fuentes, D. R., Giresi, P. G., Ng, Y. H., Marro, S., Neff, N. F. et al. (2013). Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons. Cell 155, 621-635.
260. Wassarman, K. M., Lewandoski, M., Campbell, K., Joyner, A. L., Rubenstein, J. L., Martinez, S. and Martin, G. R. (1997). Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function. Development 124, 2923-2934.
261. Weiner, W. J. (2004). Initial treatment of Parkinson disease: levodopa or dopamine agonists. Arch. Neurol. 61, 1966-1969.
262. Weinstein, D. C., Ruiz i Altaba, A., Chen, W. S., Hoodless, P., Prezioso, V. R., Jessell, T. M. and Darnell, J. E. Jr. (1994). The winged-helix transcription factor HNF-3 beta is required for notochord development in the mouse embryo. Cell 78, 575-588.
263. Xi, J., Liu, Y., Liu, H., Chen, H., Emborg, M. E. and Zhang, S.-C. (2012). Specification of midbrain dopamine neurons from primate pluripotent stem cells. Stem Cells 30, 1655-1663.
264. Xia, X. and Wong, S. T. (2012). Concise review: a high-content screening approach to stem cell research and drug discovery. Stem Cells 30, 1800-1807.
265. Xu, B., Goldman, J. S., Rymar, V. V., Forget, C., Lo, P. S., Bull, S. J., Vereker, E., Barker, P. A., Trudeau, L. E., Sadikot, A. F. et al. (2010). Critical roles for the netrin receptor deleted in colorectal cancer in dopaminergic neuronal precursor migration, axon guidance, and axon arborization. Neuroscience 169, 932-949.
266. Xue, Y., Ouyang, K., Huang, J., Zhou, Y., Ouyang, H., Li, H., Wang, G., Wu, Q., Wei, C., Bi, Y. et al. (2013). Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell 152, 82-96.
267. Yan, C. H., Levesque, M., Claxton, S., Johnson, R. L. and Ang, S.-L. (2011). Lmx1a and lmx1b function cooperatively to regulate proliferation, specification, and differentiation of midbrain dopaminergic progenitors. J. Neurosci. 31, 12413-12425.
268. Yang, J., Brown, A., Ellisor, D., Paul, E., Hagan, N. and Zervas, M. (2013a). Dynamic temporal requirement of Wnt1 in midbrain dopamine neuron development. Development 140, 1342-1352.
269. Yang, S., Edman, L. C., Sanchez-Alcaniz, J. A., Fritz, N., Bonilla, S., Hecht, J., Uhlen, P., Pleasure, S. J., Villaescusa, J. C., Marin, O. et al. (2013b). Cxcl12/ Cxcr4 signaling controls the migration and process orientation of A9-A10 dopaminergic neurons. Development 140, 4554-4564.
270. Ye, W., Shimamura, K., Rubenstein, J. L. R., Hynes, M. A. and Rosenthal, A. (1998). FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 93, 755-766.
271. Yoo, A. S., Sun, A. X., Li, L., Shcheglovitov, A., Portmann, T., Li, Y., Lee-Messer, C., Dolmetsch, R. E., Tsien, R. W. and Crabtree, G. R. (2011). MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476, 228-231.
272. Zeng, X., Cai, J., Chen, J., Luo, Y., You, Z. B., Fotter, E., Wang, Y., Harvey, B., Miura, T., Backman, C. et al. (2004). Dopaminergic differentiation of human embryonic stem cells. Stem Cells 22, 925-940.
273. Zervas, M., Millet, S., Ahn, S. and Joyner, A. L. (2004). Cell behaviors and genetic lineages of the mesencephalon and rhombomere 1. Neuron 43, 345-357.
274. Zetterström, R. H., Williams, R., Perlmann, T. and Olson, L. (1996). Cellular expression of the immediate early transcription factors Nurr1 and NGFI-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system. Brain Res. Mol. Brain Res. 41, 111-120.
275. Zetterström, R. H., Solomin, L., Jansson, L., Hoffer, B. J., Olson, L. and Perlmann, T. (1997). Dopamine neuron agenesis in Nurr1-deficient mice. Science 276, 248-250.
276. Zhang, J., Pho, V., Bonasera, S. J., Holtzman, J., Tang, A. T., Hellmuth, J., Tang, S., Janak, P. H., Tecott, L. H. and Huang, E. J. (2007). Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons. Nat. Neurosci. 10, 77-86.
277. Zou, J., Maeder, M. L., Mali, P., Pruett-Miller, S. M., Thibodeau-Beganny, S., Chou, B.-K., Chen, G., Ye, Z., Park, I.-H., Daley, G. Q. et al. (2009). Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell 5, 97-110.