Bone morphogenetic protein signalling and vertebrate nervous system development

Nature Reviews Neuroscience

Volumn 6, Issue 12, 2005, Pages 945-954

  Liu, Aimin ^a,c   Niswander, Lee A ^a,b  

^a UNIVERSITY OF COLORADO   (United States)

^b PENNSYLVANIA STATE UNIVERSITY   (United States)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN; CHORDIN; FIBROBLAST GROWTH FACTOR; FOLLISTATIN; NOGGIN; SMAD PROTEIN; SMAD4 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; WNT PROTEIN;

CELL DIFFERENTIATION; CELL FATE; CELL SPECIFICITY; ECTODERM; EMBRYONIC STEM CELL; GENETIC ANALYSIS; GRANULE CELL; LIGAND BINDING; MOLECULAR CLONING; NERVE FIBER GROWTH; NERVOUS SYSTEM DEVELOPMENT; NEURAL CREST; NEURAL TUBE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; SPINAL CORD; STRUCTURE ANALYSIS; SYNAPTIC MEMBRANE; TRANSCRIPTION INITIATION; TRANSGENIC MOUSE;

ANIMALS; BODY PATTERNING; BONE MORPHOGENETIC PROTEINS; GENE EXPRESSION; MODELS, BIOLOGICAL; NERVOUS SYSTEM; ORGANOGENESIS; SIGNAL TRANSDUCTION; VERTEBRATES;

MUS MUSCULUS; VERTEBRATA;

EID: 28644440157     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/nrn1805     Document Type: Review

References (117)

1. Nohe, A., Keating, E., Knaus, P. & Petersen, N. O. Signal transduction of bone morphogenetic protein receptors. Cell Signal. 16, 291-299 (2004).
2. Shi, Y. & Massague, J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113, 685-700 (2003).
3. Foletta, V. C. et al. Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1. J. Cell Biol. 162, 1089-1098 (2003).
4. Lee-Hoeflich, S. T. et al. Activation of LIMK1 by binding to the BMP receptor, BMPRII, regulates BMP-dependent dendritogenesis. EMBO J. 23, 4792-4801 (2004).
5. Eaton, B. A. & Davis, G. W. LIM kinase1 controls synaptic stability downstream of the type II BMP receptor. Neuron 47, 695-708 (2005).
6. Kretzschmar, M., Doody, J. & Massague, J. Opposing BMP and EGF signalling pathways converge on the TGF-β family mediator Smad1. Nature 389, 618-622 (1997).
7. Spemann, H. & Mangold, H. Uber Induktion von Embryonanlagen durch Implantation artfremder Organisatoren. Arch. Mikrosk. Anat. 100, 599-638 (1924).
8. Smith, W. C. & Harland, R. M. Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos. Cell 70, 829-840 (1992). References 8 and 10 describe the identification of noggin as a dorsalizing signal from the Spemann organizer and demonstrate that noggin functions as a BMP antagonist.
9. Smith, W. C., Knecht, A. K., Wu, M. & Harland, R. M. Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm. Nature 361, 547-549 (1993).
10. Zimmerman, L. B., De Jesus-Escobar, J. M. & Harland, R. M. The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell 86, 599-606 (1996).
11. Sasai, Y. et al. Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes. Cell 79, 779-790 (1994).
12. Piccolo, S., Sasai, Y., Lu, B. & De Robertis, E. M. Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4. Cell 86, 589-598 (1996).
13. Lamb, T. M. et al. Neural induction by the secreted polypeptide noggin. Science 262, 713-718 (1993).
14. Wilson, P. A. & Hemmati-Brivanlou, A. Induction of epidermis and inhibition of neural fate by Bmp-4. Nature 376, 331-333 (1995).
15. Sasai, Y., Lu, B., Steinbeisser, H. & De Robertis, E. M. Regulation of neural induction by the Chd and Bmp-4 antagonistic patterning signals in Xenopus. Nature 376, 333-336 (1995).
16. Hawley, S. H. et al. Disruption of BMP signals in embryonic Xenopus ectoderm leads to direct neural induction. Genes Dev. 9, 2923-2935 (1995).
17. Kuroda, H., Wessely, O. & De Robertis, E. M. Neural induction in Xenopus: requirement for ectodermal and endomesodermal signals via Chordin, Noggin, β-Catenin, and Cerberus. PLoS Biol. 2, e92 (2004).
18. Oelgeschlager, M., Kuroda, H., Reversade, B. & De Robertis, E. M. Chordin is required for the Spemann organizer transplantation phenomenon in Xenopus embryos. Dev. Cell 4, 219-230 (2003).
19. Khokha, M. K., Yeh, J., Grammer, T. C. & Harland, R. M. Depletion of three BMP antagonists from Spemann's organizer leads to a catastrophic loss of dorsal structures. Dev. Cell 8, 401-411 (2005).
20. Hild, M. et al. The smad5 mutation somitabun blocks Bmp2b signaling during early dorsoventral patterning of the zebrafish embryo. Development 126, 2149-2159 (1999).
21. Kishimoto, Y., Lee, K. H., Zon, L., Hammerschmidt, M. & Schulte-Merker, S. The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning. Development 124, 4457-4466 (1997).
22. Dick, A. et al. Essential role of Bmp7 (snailhouse) and its prodomain in dorsoventral patterning of the zebrafish embryo. Development 127, 343-354 (2000).
23. Bachiller, D. et al. The organizer factors Chordin and Noggin are required for mouse forebrain development. Nature 403, 658-661 (2000).
24. Delaune, E., Lemaire, P. & Kodjabachian, L. Neural induction in Xenopus requires early FGF signalling in addition to BMP inhibition. Development 132, 299-310 (2005).
25. Londin, E. R., Niemiec, J. & Sirotkin, H. I. Chordin, FGF signaling, and mesodermal factors cooperate in zebrafish neural induction. Dev. Biol. 279, 1-19 (2005).
26. Wilson, S. I., Graziano, E., Harland, R., Jessell, T. M. & Edlund, T. An early requirement for FGF signalling in the acquisition of neural cell fate in the chick embryo. Curr. Biol. 10, 421-429 (2000).
27. Streit, A., Berliner, A. J., Papanayotou, C., Sirulnik, A. & Stern, C. D. Initiation of neural induction by FGF signalling before gastrulation. Nature 406, 74-78 (2000).
28. Lamb, T. M. & Harland, R. M. Fibroblast growth factor is a direct neural inducer, which combined with noggin generates anterior-posterior neural pattern. Development 121, 3627-3636 (1995).
29. Launay, C., Fromentoux, V., Shi, D. L. & Boucaut, J. C. A truncated FGF receptor blocks neural induction by endogenous Xenopus inducers. Development 122, 869-880 (1996).
30. Pera, E. M., Wessely, O., Li, S. Y. & De Robertis, E. M. Neural and head induction by insulin-like growth factor signals. Dev. Cell 1, 655-665 (2001).
31. Pera, E. M., Ikeda, A., Eivers, E. & De Robertis, E. M. Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. Genes Dev. 17, 3023-3028 (2003). Shows that Smad1 phosphorylation by MAPK, which is activated by the IGF and FGF pathways, is crucial for the neural inhibiting activity of BMP, providing the molecular basis for the crosstalk between these signalling pathways.
32. Farlie, P. G., McKeown, S. J. & Newgreen, D. F. The neural crest: basic biology and clinical relationships in the craniofacial and enteric nervous systems. Birth Defects Res. C Embryo Today 72, 173-189 (2004).
33. Selleck, M. A. & Bronner-Fraser, M. Origins of the avian neural crest: the role of neural plate-epidermal interactions. Development 121, 525-538 (1995).
34. Moury J. D. & Jacobson, A. G. The origins of neural crest cells in the axolotl. Dev. Biol. 141, 243-253 (1990).
35. Moury, J. D. & Jacobson, A. G. Neural fold formation at newly created boundaries between neural plate and epidermis in the axolotl. Dev. Biol. 133, 44-57 (1989).
36. Dickinson, M. E., Selleck, M. A., McMahon, A. P. & Bronner-Fraser, M. Dorsalization of the neural tube by the non-neural ectoderm. Development 121, 2099-2106 (1995).
37. Liem, K. F. Jr, Tremml, G., Roelink, H. & Jessell, T. M. Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm. Cell 82, 969-979 (1995).
38. Schmid, B. et al. Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation. Development 127, 957-967 (2000).
39. Nguyen, V. H. et al. Dorsal and intermediate neuronal cell types of the spinal cord are established by a BMP signaling pathway. Development 127, 1209-1220 (2000). Describes the analysis of three zebrafish mutants (swr, snh and sbn) that have defective BMP signalling and shows that BMP signalling is essential for spinal cord patterning and neural crest induction. The authors also show that cell fates in the spinal cord are determined by a BMP gradient.
40. Nguyen, V. H. et al. Ventral and lateral regions of the zebrafish gastrula, including the neural crest progenitors, are established by a bmp2b/swirl pathway of genes. Dev. Biol. 199, 93-110 (1998).
41. Saint-Jeannet, J. P., He, X., Varmus, H. E. & Dawid, I. B. Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a. Proc. Natl Acad. Sci. USA 94, 13713-13718 (1997).
42. Chang, C. & Hemmati-Brivanlou, A. Neural crest induction by Xwnt7B in Xenopus. Dev. Biol. 194, 129-134 (1998).
43. LaBonne, C. & Bronner-Fraser, M. Neural crest induction in Xenopus: evidence for a two-signal model. Development 125, 2403-2414 (1998).
44. Deardorff, M. A., Tan, C., Saint-Jeannet, J. P. & Klein, P. S. A role for frizzled 3 in neural crest development. Development 128, 3655-3663 (2001).
45. Bang, A. G., Papalopulu, N., Goulding, M. D. & Kintner, C. Expression of Pax-3 in the lateral neural plate is dependent on a Wnt-mediated signal from posterior nonaxial mesoderm. Dev. Biol. 212, 366-380 (1999).
46. Ikeya, M., Lee, S. M., Johnson, J. E., McMahon, A. P. & Takada, S. Wnt signalling required for expansion of neural crest and CNS progenitors. Nature 389, 966-970 (1997).
47. Garcia-Castro, M. & Bronner-Fraser, M. Induction and differentiation of the neural crest. Curr. Opin. Cell Biol. 11, 695-698 (1999).
48. Lewis, J. L. et al. Reiterated Wnt signaling during zebrafish neural crest development. Development 131, 1299-1308 (2004).
49. Monsoro-Burq, A. H., Wang, E. & Harland, R. Msx1 and Pax3 cooperate to mediate FGF8 and WNT signals during Xenopus neural crest induction. Dev. Cell 8, 167-178 (2005).
50. Monsoro-Burq, A. H., Fletcher, R. B. & Harland, R. M. Neural crest induction by paraxial mesoderm in Xenopus embryos requires FGF signals. Development 130, 3111-3124 (2003).
51. Sela-Donenfeld, D. & Kalcheim, C. Regulation of the onset of neural crest migration by coordinated activity of BMP4 and Noggin in the dorsal neural tube. Development 126, 4749-4762 (1999).
52. Sela-Donenfeld, D. & Kalcheim, C. Inhibition of noggin expression in the dorsal neural tube by somitogenesis: a mechanism for coordinating the timing of neural crest emigration. Development 127, 4845-4854 (2000).
53. Graham, A., Francis-West, P., Brickell, P. & Lumsden, A. The signalling molecule BMP4 mediates apoptosis in the rhombencephalic neural crest. Nature 372, 684-686 (1994).
54. Marazzi, G., Wang, Y. & Sassoon, D. Msx2 is a transcriptional regulator in the BMP4-mediated programmed cell death pathway. Dev. Biol. 186, 127-138 (1997).
55. Smith, A. & Graham, A. Restricting Bmp-4 mediated apoptosis in hindbrain neural crest. Dev. Dyn. 220, 276-283 (2001).
56. Shah, N. M., Groves, A. K. & Anderson, D. J. Alternative neural crest cell fates are instructively promoted by TGFβ superfamily members. Cell 85, 331-343 (1996).
57. Varley, J. E., McPherson, C. E., Zou, H., Niswander, L. & Maxwell, G. D. Expression of a constitutively active type I BMP receptor using a retroviral vector promotes the development of adrenergic cells in neural crest cultures. Dev. Biol. 196, 107-118 (1998).
58. Varley, J. E. & Maxwell, G. D. BMP-2 and BMP-4, but not BMP-6, increase the number of adrenergic cells which develop in quail trunk neural crest cultures. Exp. Neurol. 140, 84-94 (1996).
59. Burstyn-Cohen, T., Stanleigh, J., Sela-Donenfeld, D. & Kalcheim, C. Canonical Wnt activity regulates trunk neural crest delamination linking BMP/noggin signaling with G1/S transition. Development 131, 5327-5339 (2004).
60. de Melker, A. A., Desban, N. & Duband, J. L. Cellular localization and signaling activity of β-catenin in migrating neural crest cells. Dev. Dyn. 230, 708-726 (2004).
61. Hari, L. et al. Lineage-specific requirements of β-catenin in neural crest development. J. Cell Biol. 159, 867-880 (2002).
62. Kleber, M. et al. Neural crest stem cell maintenance by combinatorial Wnt and BMP signaling. J. Cell Biol. 169, 309-320 (2005).
63. Goulding, M. D., Chalepakis, G., Deutsch, U., Erselius, J. R. & Gruss, P. Pax-3, a novel murine DNA binding protein expressed during early neurogenesis. EMBO J. 10, 1135-1147 (1991).
64. Jostes, B., Walther, C. & Gruss, P. The murine paired box gene, Pax7, is expressed specifically during the development of the nervous and muscular system. Mech. Dev. 33, 27-37 (1990).
65. Walther, C. & Gruss, P. Pax-6, a murine paired box gene, is expressed in the developing CNS. Development 113, 1435-1449 (1991).
66. Briscoe, J. et al. Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature 398, 622-627 (1999).
67. Lee, K. J., Mendelsohn, M. & Jessell, T. M. Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord. Genes Dev. 12, 3394-3407 (1998).
68. Basler, K., Edlund, T., Jessell, T. M. & Yamada, T. Control of cell pattern in the neural tube: regulation of cell differentiation by dorsalin-1, a novel TGF β family member. Cell 73, 687-702 (1993).
69. Lee, K. J., Dietrich, P. & Jessell, T. M. Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification. Nature 403, 734-740 (2000).
70. Millonig, J. H., Millen, K. J. & Hatten, M. E. The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS. Nature 403, 764-769 (2000).
71. Liem, K. F. Jr, Tremml, G. & Jessell, T. M. A role for the roof plate and its resident TGFβ-related proteins in neuronal patterning in the dorsal spinal cord. Cell 91, 127-138 (1997). Using an intermediate spinal cord explant assay, the authors showed that the roof plate provides signals that regulate dorsal spinal cord patterning. Furthermore, TGFβ proteins, including BMPs, which are expressed by roof plate cells, can mediate this activity.
72. Timmer, J. R., Wang, C. & Niswander, L. BMP signaling patterns the dorsal and intermediate neural tube via regulation of homeobox and helix-loop-helix transcription factors. Development 129, 2459-2472 (2002). Provides in vivo evidence that BMP signalling is essential for patterning the dorsal and intermediate spinal cord in the chick embryo.
73. Panchision, D. M. et al. Sequential actions of BMP receptors control neural precursor cell production and fate. Genes Dev. 15, 2094-2110 (2001).
74. Chesnutt, C., Burrus, L. W., Brown, A. M. & Niswander, L. Coordinate regulation of neural tube patterning and proliferation by TGFβ and WNT activity. Dev. Biol. 274, 334-347 (2004).
75. Timmer, J., Chesnutt, C. & Niswander, L. The Activin signaling pathway promotes differentiation of dl3 interneurons in the spinal neural tube. Dev. Biol. 285, 1-10 (2005).
76. Wine-Lee, L. et al. Signaling through BMP type 1 receptors is required for development of interneuron cell types in the dorsal spinal cord. Development 131, 5393-5403 (2004).
77. Chiang, C. et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407-413 (1996).
78. McMahon, J. A. et al. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev. 12, 1438-1452 (1998).
79. Liem, K. F. Jr, Jessell, T. M. & Briscoe, J. Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites. Development 127, 4855-4866 (2000).
80. Mekki-Dauriac, S., Agius, E., Kan, P. & Cochard, P. Bone morphogenetic proteins negatively control oligodendrocyte precursor specification in the chick spinal cord. Development 129, 5117-5130 (2002).
81. Hammerschmidt, M., Serbedzija, G. N. & McMahon, A. P. Genetic analysis of dorsoventral pattern formation in the zebrafish: requirement of a BMP-like ventralizing activity and its dorsal repressor. Genes Dev. 10, 2452-2461 (1996).
82. Hatta, K., Kimmel, C. B., Ho, R. K. & Walker, C. The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system. Nature 350, 339-341 (1991).
83. Strahle, U. et al. one-eyed pinhead is required for development of the ventral midline of the zebrafish (Danio rerio) neural tube. Genes Funct. 1, 131-148 (1997).
84. Albert, S. et al. Cyclops-independent floor plate differentiation in zebrafish embryos. Dev. Dyn. 226, 59-66 (2003).
85. Gritsman, K. et al. The EGF-CFC protein one-eyed pinhead is essential for nodal signaling. Cell 97, 121-132 (1999).
86. Rebagliati, M. R., Toyama, R., Haffter, P. & Dawid, I. B. cyclops encodes a nodal-related factor involved in midline signaling. Proc. Natl Acad. Sci. USA 95, 9932-9937 (1998).
87. Sampath, K. et al. Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling. Nature 395, 185-189 (1998).
88. Feldman, B. et al. Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature 395, 181-185 (1998).
89. Megason, S. G. & McMahon, A. P. A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. Development 129, 2087-2098 (2002).
90. Zechner, D. et al. β-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. Dev. Biol. 258, 406-418 (2003).
91. Butler, S. J. & Dodd, J. A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons. Neuron 38, 389-401 (2003).
92. Augsburger, A., Schuchardt, A., Hoskins, S., Dodd, J. & Butler, S. BMPs as mediators of roof plate repulsion of commissural neurons. Neuron 24, 127-141 (1999). Together, references 91 and 92 showed that BMP proteins secreted by the roof plate have pivotal roles in guiding the commissural axons.
93. Furuta, Y., Piston, D. W. & Hogan, B. L. Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development 124, 2203-2212 (1997).
94. Anderson, R. M., Lawrence, A. R., Stottmann, R. W., Bachiller, D. & Klingensmith, J. Chordin and noggin promote organizing centers of forebrain development in the mouse. Development 129, 4975-4987 (2002).
95. Hebert, J. M., Mishina, Y. & McConnell, S. K. BMP signaling is required locally to pattern the dorsal telencephalic midline. Neuron 35, 1029-1041 (2002).
96. D'Alessandro, J. S. & Wang, E. A. Bone morphogenetic proteins inhibit proliferation, induce reversible differentiation and prevent cell death in astrocyte lineage cells. Growth Factors 11, 45-52 (1994).
97. D'Alessandro, J. S., Yetz-Aldape, J. & Wang, E. A. Bone morphogenetic proteins induce differentiation in astrocyte lineage cells. Growth Factors 11, 53-69 (1994).
98. Gomes, W. A., Mehler, M. F. & Kessler, J. A. Transgenic overexpression of BMP4 increases astroglial and decreases oligodendroglial lineage commitment. Dev. Biol. 255, 164-177 (2003).
99. Gross, R. E. et al. Bone morphogenetic proteins promote astroglial lineage commitment by mammalian subventricular zone progenitor cells. Neuron 17, 595-606 (1996).
100. Mehler, M. F., Mabie, P. C., Zhu, G., Gokhan, S. & Kessler, J. A. Developmental changes in progenitor cell responsiveness to bone morphogenetic proteins differentially modulate progressive CNS lineage fate. Dev. Neurosci. 22, 74-85 (2000).
101. Grinspan, J. B. et al. Stage-specific effects of bone morphogenetic proteins on the oligodendrocyte lineage. J. Neurobiol. 43, 1-17 (2000).
102. Mabie, P. C. et al. Bone morphogenetic proteins induce astroglial differentiation of oligodendroglial-astroglial progenitor cells. J. Neurosci. 17, 4112-4120 (1997).
103. Alder, J., Lee, K. J., Jessell, T. M. & Hatten, M. E. Generation of cerebellar granule neurons in vivo by transplantation of BMP-treated neural progenitor cells. Nature Neurosci. 2, 535-540 (1999). Using both in vitro explant assays and in vivo cell transplantion, the authors showed that BMP signalling is crucial for the determination of cerebellar granule neurons.
104. Rios, I., Alvarez-Rodriguez, R., Marti, E. & Pons, S. Bmp2 antagonizes sonic hedgehog-mediated proliferation of cerebellar granule neurones through Smad5 signalling. Development 131, 3159-3168 (2004).
105. Angley, C., Kumar, M., Dinsio, K. J., Hall, A. K. & Siegel, R. E. Signaling by bone morphogenetic proteins and Smad1 modulates the postnatal differentiation of cerebellar cells. J. Neurosci. 23, 260-268 (2003).
106. Meng, Y. et al. Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron 35, 121-133 (2002).
107. Endo, M. et al. Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin. J. Neurosci. 23, 2527-2537 (2003).
108. Suzuki, A., Ueno, N. & Hemmati-Brivanlou, A. Xenopus msx1 mediates epidermal induction and neural inhibition by BMP4. Development 124, 3037-3044 (1997).
109. Binato, R., Martinez, C. E., Pizzatti, L., Robert, B. & Abdelhay, E. SMAD 8 binding to mice Msx-1 basal promoter is required for transcriptional activation. Biochem. J. 16 Aug 2005 (doi: 10.1042/BJ20050327).
110. Alvarez Martinez, C. E. et al. Characterization of a Smad motif similar to Drosophila mad in the mouse Msx1 promoter. Biochem. Biophys. Res. Commun. 291, 655-662 (2002).
111. Liu, Y., Helms, A. W. & Johnson, J. E. Distinct activities of Msx1 and Msx3 in dorsal neural tube development. Development 131, 1017-1028 (2004).
112. Tribulo, C., Aybar, M. J., Nguyen, V. H., Mullins, M. C. & Mayor, R. Regulation of Msx genes by a Bmp gradient is essential for neural crest specification. Development 130, 6441-6452 (2003).
113. Bach, A. et al. Msx1 is required for dorsal diencephalon patterning. Development 130, 4025-4036 (2003).
114. Fernandez-Llebrez, P. et al. Msx1-deficient mice fail to form prosomere 1 derivatives, subcommissural organ, and posterior commissure and develop hydrocephalus. J. Neuropathol. Exp. Neurol. 63, 574-586 (2004).
115. Ramos, C., Fernandez-Llebrez, P., Bach, A., Robert, B. & Soriano, E. Msx1 disruption leads to diencephalon defects and hydrocephalus. Dev. Dyn. 230, 446-460 (2004).
116. Linker, C. & Stern, C. D. Neural induction requires BMP inhibition only as a late step, and involves signals other than FGF and Wnt antagonists. Development 131, 5671-5681 (2004).
117. Hussein, S. M., Duff, E. K. & Sirard, C. Smad4 and β-catenin co-activators functionally interact with lymphoid-enhancing factor to regulate graded expression of Msx2. J. Biol. Chem. 278, 48805-48814 (2003).