The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex

Seminars in Cell and Developmental Biology

Volumn 52, Issue , 2016, Pages 12-20

  Tee, Andrew R ^a   Sampson, Julian R ^a   Pal, Deb K ^b   Bateman, Joseph M ^b  

^a CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

^b KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Epilepsy; mTOR; Neural stem cell; Neuronal differentiation; Neuronal migration; TSC

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; STRESS ACTIVATED PROTEIN KINASE 1; TARGET OF RAPAMYCIN KINASE;

ANIMAL MODEL; CELL DIFFERENTIATION; CELL MIGRATION; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; EPILEPSY; EPISTASIS; GENE CONTROL; GENE MUTATION; GENETIC CODE; HUMAN; MIGRATION; MONOGENIC DISORDER; NERVE CELL DIFFERENTIATION; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; TUBEROUS SCLEROSIS COMPLEX; ANIMAL; DISEASE MODEL; ENZYMOLOGY; GENETICS; METABOLISM; PATHOLOGY; TUBEROUS SCLEROSIS;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; NEUROGENESIS; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TUBEROUS SCLEROSIS;

EID: 84961209822     PISSN: 10849521     EISSN: 10963634     Source Type: Journal    
DOI: 10.1016/j.semcdb.2016.01.040     Document Type: Review

References (88)

1. Curatolo P., Moavero R., de Vries P.J. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol. 2015, 14:733-745.
2. Costa-Mattioli M., Monteggia L.M. mTOR complexes in neurodevelopmental and neuropsychiatric disorders. Nat. Neurosci. 2013, 16:1537-1543.
3. Feliciano D.M., Lin T.V., Hartman N.W., Bartley C.M., Kubera C., Hsieh L., et al. A circuitry and biochemical basis for tuberous sclerosis symptoms: from epilepsy to neurocognitive deficits. Int. J. Dev. Neurosci. 2013, 31:667-678.
4. Lipton J.O., Sahin M. The neurology of mTOR. Neuron 2014, 84:275-291.
5. O'Callaghan F.J., Shiell A.W., Osborne J.P., Martyn C.N. Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet 1998, 351:1490.
6. Consortium E.C.T.S. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 1993, 75:1305-1315.
7. van Slegtenhorst M., de Hoogt R., Hermans C., Nellist M., Janssen B., Verhoef S., et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 1997, 277:805-808.
8. Dibble C.C., Elis W., Menon S., Qin W., Klekota J., Asara J.M., et al. TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol. Cell 2012, 47:535-546.
9. Orlova K.A., Crino P.B. The tuberous sclerosis complex. Ann. NY Acad. Sci. 2010, 1184:87-105.
10. Jansen F.E., van Huffelen A.C., Algra A., van Nieuwenhuizen O. Epilepsy surgery in tuberous sclerosis: a systematic review. Epilepsia 2007, 48:1477-1484.
11. Bender B.L., Yunis E.J. Central nervous system pathology of tuberous sclerosis in children. Ultrastruct. Pathol. 1980, 1:287-299.
12. Ess K.C., Kamp C.A., Tu B.P., Gutmann D.H. Developmental origin of subependymal giant cell astrocytoma in tuberous sclerosis complex. Neurology 2005, 64:1446-1449.
13. Shepherd C.W., Gomez M.R., Lie J.T., Crowson C.S. Causes of death in patients with tuberous sclerosis. Mayo Clin. Proc. 1991, 66:792-796.
14. Wortmann S.B., Reimer A., Creemers J.W., Mullaart R.A. Prenatal diagnosis of cerebral lesions in tuberous sclerosis complex (TSC): case report and review of the literature. Eur. J. Paediatr. Neurol. 2008, 12:123-126.
15. Park S.H., Pepkowitz S.H., Kerfoot C., De Rosa M.J., Poukens V., Wienecke R., et al. Tuberous sclerosis in a 20-week gestation fetus: immunohistochemical study. Acta Neuropathol. 1997, 94:180-186.
16. Tsai V., Parker W.E., Orlova K.A., Baybis M., Chi A.W., Berg B.D., et al. Fetal brain mTOR signaling activation in tuberous sclerosis complex. Cereb. Cortex (New York, N.Y.: 1991) 2014, 24:315-327.
17. Zoncu R., Efeyan A., Sabatini D.M. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 2011, 12:21-35.
18. Manning B.D., Tee A.R., Logsdon M.N., Blenis J., Cantley L.C. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 2002, 10:151-162.
19. Tee A.R., Fingar D.C., Manning B.D., Kwiatkowski D.J., Cantley L.C., Blenis J. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:13571-13576.
20. Dunlop E.A., Dodd K.M., Seymour L.A., Tee A.R. Mammalian target of rapamycin complex 1-mediated phosphorylation of eukaryotic initiation factor 4E-binding protein 1 requires multiple protein-protein interactions for substrate recognition. Cell. Signal. 2009, 21:1073-1084.
21. Tee A.R., Anjum R., Blenis J. Inactivation of the tuberous sclerosis complex -1 and -2 gene products occurs by phosphoinositide 3-kinase/Akt-dependent and -independent phosphorylation of tuberin. J. Biol. Chem. 2003, 278:37288-37296.
22. Ballif B.A., Roux P.P., Gerber S.A., MacKeigan J.P., Blenis J., Gygi S.P. Quantitative phosphorylation profiling of the ERK/p90 ribosomal S6 kinase-signaling cassette and its targets, the tuberous sclerosis tumor suppressors. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:667-672.
23. Kim D.H., Sarbassov D.D., Ali S.M., Latek R.R., Guntur K.V., Erdjument-Bromage H., et al. GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol. Cell 2003, 11:895-904.
24. Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 2010, 141:290-303.
25. Tee A.R., Manning B.D., Roux P.P., Cantley L.C., Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr. Biol. 2003, 13:1259-1268.
26. Dodd K.M., Dunlop E.A. Tuberous sclerosis-a model for tumour growth. Semin. Cell Dev. Biol. 2016, in press. 10.1016/j.semcdb.2016.01.025.
27. Holz M.K., Ballif B.A., Gygi S.P., Blenis J. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell 2005, 123:569-580.
28. Chauvin C., Koka V., Nouschi A., Mieulet V., Hoareau-Aveilla C., Dreazen A., et al. Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program. Oncogene 2014, 33:474-483.
29. Ben-Sahra I., Howell J.J., Asara J.M., Manning B.D. Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. Science 2013, 339:1323-1328.
30. Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005, 307:1098-1101.
31. Garcia-Martinez J.M., Alessi D.R. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem. J. 2008, 416:375-385.
32. Ikenoue T., Inoki K., Yang Q., Zhou X., Guan K.L. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J. 2008, 27:1919-1931.
33. Franco S.J., Muller U. Shaping our minds: stem and progenitor cell diversity in the mammalian neocortex. Neuron 2013, 77:19-34.
34. Haubensak W., Attardo A., Denk W., Huttner W.B. Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:3196-3201.
35. Ka M., Condorelli G., Woodgett J.R., Kim W.Y. mTOR regulates brain morphogenesis by mediating GSK3 signaling. Development 2014, 141:4076-4086.
36. Hartman N.W., Lin T.V., Zhang L., Paquelet G.E., Feliciano D.M., Bordey A. mTORC1 targets the translational repressor 4E-BP2, but not S6 kinase 1/2, to regulate neural stem cell self-renewal in vivo. Cell Rep. 2013, 5:433-444.
37. Hentges K., Thompson K., Peterson A. The flat-top gene is required for the expansion and regionalization of the telencephalic primordium. Development 1999, 126:1601-1609.
38. Hentges K.E., Sirry B., Gingeras A.C., Sarbassov D., Sonenberg N., Sabatini D., et al. FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:1801-13796.
39. Sato A., Sunayama J., Matsuda K., Tachibana K., Sakurada K., Tomiyama A., et al. Regulation of neural stem/progenitor cell maintenance by PI3K and mTOR. Neurosci. Lett. 2010, 470:115-120.
40. Love N.K., Keshavan N., Lewis R., Harris W.A., Agathocleous M. A nutrient-sensitive restriction point is active during retinal progenitor cell differentiation. Development 2014, 141:697-706.
41. Gangloff Y.G., Mueller M., Dann S.G., Svoboda P., Sticker M., Spetz J.F., et al. Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development. Mol. Cell Biol. 2004, 24:9508-9516.
42. Murakami M., Ichisaka T., Maeda M., Oshiro N., Hara K., Edenhofer F., et al. mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells. Mol. Cell Biol. 2004, 24:6710-6718.
43. Cloetta D., Thomanetz V., Baranek C., Lustenberger R.M., Lin S., Oliveri F., et al. Inactivation of mTORC1 in the developing brain causes microcephaly and affects gliogenesis. J. Neurosci. 2013, 33:7799-7810.
44. Zou J., Zhou L., Du X.X., Ji Y., Xu J., Tian J., et al. Rheb1 is required for mTORC1 and myelination in postnatal brain development. Dev. Cell 2011, 20:97-108.
45. Magri L., Cominelli M., Cambiaghi M., Cursi M., Leocani L., Minicucci F., et al. Timing of mTOR activation affects tuberous sclerosis complex neuropathology in mouse models. Dis. Models Mech. 2013, 6:1185-1197.
46. Way S.W., McKenna J., Mietzsch U., Reith R.M., Wu H.C., Gambello M.J. Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse. Hum. Mol. Genet. 2009, 18:1252-1265.
47. Magri L., Cambiaghi M., Cominelli M., Alfaro-Cervello C., Cursi M., Pala M., et al. Sustained activation of mTOR pathway in embryonic neural stem cells leads to development of tuberous sclerosis complex-associated lesions. Cell Stem Cell 2011, 9:447-462.
48. Crino P.B. Molecular pathogenesis of tuber formation in tuberous sclerosis complex. J. Child Neurol. 2004, 19:716-725.
49. Feliciano D.M., Quon J.L., Su T., Taylor M.M., Bordey A. Postnatal neurogenesis generates heterotopias, olfactory micronodules and cortical infiltration following single-cell Tsc1 deletion. Hum. Mol. Genet. 2012, 21:799-810.
50. Lafourcade C.A., Lin T.V., Feliciano D.M., Zhang L., Hsieh L.S., Bordey A. Rheb activation in subventricular zone progenitors leads to heterotopia, ectopic neuronal differentiation, and rapamycin-sensitive olfactory micronodules and dendrite hypertrophy of newborn neurons. J. Neurosci. 2013, 33:2419-2431.
51. Zhou J., Shrikhande G., Xu J., McKay R.M., Burns D.K., Johnson J.E., et al. Tsc1 mutant neural stem/progenitor cells exhibit migration deficits and give rise to subependymal lesions in the lateral ventricle. Genes Dev. 2011, 25:1595-1600.
52. Malagelada C., Lopez-Toledano M.A., Willett R.T., Jin Z.H., Shelanski M.L., Greene L.A. RTP801/REDD1 regulates the timing of cortical neurogenesis and neuron migration. J. Neurosci. 2011, 31:3186-3196.
53. Zhu G., Chow L.M., Bayazitov I.T., Tong Y., Gilbertson R.J., Zakharenko S.S., et al. Pten deletion causes mTorc1-dependent ectopic neuroblast differentiation without causing uniform migration defects. Development 2012, 139:3422-3431.
54. Lee A., Maldonado M., Baybis M., Walsh C.A., Scheithauer B., Yeung R., et al. Markers of cellular proliferation are expressed in cortical tubers. Ann. Neurol. 2003, 53:668-673.
55. Mizuguchi M., Takashima S. Neuropathology of tuberous sclerosis. Brain Dev. 2001, 23:508-515.
56. Yamanouchi H., Jay V., Rutka J.T., Takashima S., Becker L.E. Evidence of abnormal differentiation in giant cells of tuberous sclerosis. Pediatr. Neurol. 1997, 17:49-53.
57. Bateman J.M., McNeill H. Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila. Cell 2004, 119:87-96.
58. Bateman J.M., McNeill H. Insulin/IGF signalling in neurogenesis. Cell. Mol. Life Sci. 2006, 63:1701-1705.
59. McNeill H., Craig G.M., Bateman J.M. Regulation of neurogenesis and epidermal growth factor receptor signaling by the insulin receptor/target of rapamycin pathway in Drosophila. Genetics 2008, 179:843-853.
60. Avet-Rochex A., Carvajal N., Christoforou C.P., Yeung K., Maierbrugger K.T., Hobbs C., et al. Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control. PLoS Genet. 2014, 10:e1004624.
61. Jones I., Hagglund A.C., Tornqvist G., Nord C., Ahlgren U., Carlsson L. A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development. Dis.Models Mech. 2015, 8:1517-1529.
62. Han J., Wang B., Xiao Z., Gao Y., Zhao Y., Zhang J., et al. Mammalian target of rapamycin (mTOR) is involved in the neuronal differentiation of neural progenitors induced by insulin. Mol. Cell. Neurosci. 2008, 39:118-124.
63. Fishwick K.J., Li R.A., Halley P., Deng P., Storey K.G. Initiation of neuronal differentiation requires PI3-kinase/TOR signalling in the vertebrate neural tube. Dev. Biol. 2010, 338:215-225.
64. Chang B.S., Lowenstein D.H. Epilepsy. N. Engl. J. Med. 2003, 349:1257-1266.
65. Andres-Mach M., Fike J.R., Luszczki J.J. Neurogenesis in the epileptic brain: a brief overview from temporal lobe epilepsy. Pharmacol. Rep. 2011, 63:1316-1323.
66. Cho K.O., Lybrand Z.R., Ito N., Brulet R., Tafacory F., Zhang L., et al. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nat. Commun. 2015, 6:6606.
67. Yu T.S., Zhang G., Liebl D.J., Kernie S.G. Traumatic brain injury-induced hippocampal neurogenesis requires activation of early nestin-expressing progenitors. J. Neurosci. 2008, 28:12901-12912.
68. Zeng L.H., Rensing N.R., Wong M. The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy. J. Neurosci. 2009, 29:6964-6972.
69. Buckmaster P.S., Ingram E.A., Wen X. Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy. J. Neurosci. 2009, 29:8259-8269.
70. Macias M., Blazejczyk M., Kazmierska P., Caban B., Skalecka A., Tarkowski B., et al. Spatiotemporal characterization of mTOR kinase activity following kainic acid induced status epilepticus and analysis of rat brain response to chronic rapamycin treatment. PLoS One 2013, 8:e64455.
71. Russo E., Follesa P., Citraro R., Camastra C., Donato A., Isola D., et al. The mTOR signaling pathway and neuronal stem/progenitor cell proliferation in the hippocampus are altered during the development of absence epilepsy in a genetic animal model. Neurol. Sci. 2014, 35:1793-1799.
72. Abs E., Goorden S.M., Schreiber J., Overwater I.E., Hoogeveen-Westerveld M., Bruinsma C.F., et al. TORC1-dependent epilepsy caused by acute biallelic Tsc1 deletion in adult mice. Ann. Neurol. 2013, 74:569-579.
73. Saxena A., Sampson J.R. Phenotypes associated with inherited and developmental somatic mutations in genes encoding mTOR pathway components. Semin. Cell Dev. Biol. 2014, 36:140-146.
74. Puffenberger E.G., Strauss K.A., Ramsey K.E., Craig D.W., Stephan D.A., Robinson D.L., et al. Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5. Brain 2007, 130:1929-1941.
75. Dibbens L.M., de Vries B., Donatello S., Heron S.E., Hodgson B.L., Chintawar S., et al. Mutations in DEPDC5 cause familial focal epilepsy with variable foci. Nat. Genet. 2013, 45:546-551.
76. Ishida S., Picard F., Rudolf G., Noe E., Achaz G., Thomas P., et al. Mutations of DEPDC5 cause autosomal dominant focal epilepsies. Nat. Genet. 2013, 45:552-555.
77. Striano P., Serioli E., Santulli L., Manna I., Labate A., Dazzo E., et al. DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy. Epilepsia 2015.
78. J.S. Lim, W.I. Kim, H.C. Kang, S.H. Kim. Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy 21 (2015) 395-400.
79. Leventer R.J., Scerri T., Marsh A.P., Pope K., Gillies G., Maixner W., et al. Hemispheric cortical dysplasia secondary to a mosaic somatic mutation in MTOR. Neurology 2015, 84:2029-2032.
80. Nakashima M., Saitsu H., Takei N., Tohyama J., Kato M., Kitaura H., et al. Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb. Ann. Neurol. 2015, 78:375-386.
81. Scerri T., Riseley J.R., Gillies G., Pope K., Burgess R., Mandelstam S.A., et al. Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5. Ann. Clini. Trans. Neurol. 2015, 2:575-580.
82. Lee J.H., Huynh M., Silhavy J.L., Kim S., Dixon-Salazar T., Heiberg A., et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat. Genet. 2012, 44:941-945.
83. D'Gama A.M., Geng Y., Couto J.A., Martin B., Boyle E.A., LaCoursiere C.M., et al. Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia. Ann. Neurol. 2015, 77:720-725.
84. Allen A.S., Berkovic S.F., Cossette P., Delanty N., Dlugos D., Eichler E.E., et al. De novo mutations in epileptic encephalopathies. Nature 2013, 501:217-221.
85. Murn J., Zarnack K., Yang Y.J., Durak O., Murphy E.A., Cheloufi S., et al. Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt. Genes Dev. 2015, 29:501-512.
86. Avet-Rochex A., Kaul A.K., Gatt A.P., McNeill H., Bateman J.M. Concerted control of gliogenesis by InR/TOR and FGF signalling in the Drosophila post-embryonic brain. Development 2012, 139:2763-2772.
87. Avet-Rochex A., Maierbrugger K.T., Bateman J.M. Glial enriched gene expression profiling identifies novel factors regulating the proliferation of specific glial subtypes in the Drosophila brain. Gene Expr. Patterns 2014, 16:61-68.
88. Carson R.P., Van Nielen D.L., Winzenburger P.A., Ess K.C. Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin. Neurobiol. Dis. 2012, 45:369-380.