Knockdown of Human TCF4 Affects Multiple Signaling Pathways Involved in Cell Survival, Epithelial to Mesenchymal Transition and Neuronal Differentiation

PLoS ONE

Volumn 8, Issue 8, 2013, Pages

  Forrest, Marc P ^a   Waite, Adrian J ^a   Martin Rendon, Enca ^b,c   Blake, Derek J ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c JOHN RADCLIFFE HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

SMALL INTERFERING RNA; TRANSFORMING GROWTH FACTOR BETA;

APOPTOSIS; ARTICLE; ASCL1 GENE; CELL SURVIVAL; CONTROLLED STUDY; DEC1 GENE; DOWN REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; GENE; GENE DELETION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE IDENTIFICATION; GENE SILENCING; MEF2C GENE; MICROARRAY ANALYSIS; NERVE CELL CULTURE; NERVE CELL DIFFERENTIATION; NEUROBLASTOMA CELL; NEUROG2 GENE; NUCLEOTIDE SEQUENCE; SIGNAL TRANSDUCTION; SNAI2 GENE; TRANSCRIPTION FACTOR 4 GENE; UBE3A GENE; UPREGULATION; ZEB2 GENE;

ANGELMAN SYNDROME; BASIC HELIX-LOOP-HELIX LEUCINE ZIPPER TRANSCRIPTION FACTORS; CELL LINE, TUMOR; CELL SURVIVAL; EPITHELIAL-MESENCHYMAL TRANSITION; FACIES; GENE EXPRESSION REGULATION; GENE KNOCKDOWN TECHNIQUES; GENOME-WIDE ASSOCIATION STUDY; HIRSCHSPRUNG DISEASE; HUMANS; INTELLECTUAL DISABILITY; MICROCEPHALY; NEUROGENESIS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 84882960508     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0073169     Document Type: Article

References (61)

1. Navarrete K, Pedroso I, De Jong S, Stefansson H, Steinberg S, et al. (2013) TCF4 (e2-2; ITF2): A schizophrenia-associated gene with pleiotropic effects on human disease. Am J Med Genet B Neuropsychiatr Genet 162: 1-16. doi:10.1002/ajmg.b.32109. PubMed: 23129290.
2. Reizis B, (2010) Regulation of plasmacytoid dendritic cell development. Curr Opin Immunol 22: 206-211. doi:10.1016/j.coi.2010.01.005. PubMed: 20144853.
3. Murre C, (2005) Helix-loop-helix proteins and lymphocyte development. Nat Immunol 6: 1079-1086. doi:10.1038/ni1260. PubMed: 16239924.
4. Henthorn P, Kiledjian M, Kadesch T, (1990) Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif. Science 247: 467-470. doi:10.1126/science.2105528. PubMed: 2105528.
5. Flora A, Garcia JJ, Thaller C, Zoghbi HY, (2007) The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors. Proc Natl Acad Sci U S A 104: 15382-15387. doi:10.1073/pnas.0707456104. PubMed: 17878293.
6. Zweier C, Peippo MM, Hoyer J, Sousa S, Bottani A, et al. (2007) Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome). Am J Hum Genet 80: 994-1001. doi:10.1086/515583. PubMed: 17436255.
7. Amiel J, Rio M, de Pontual L, Redon R, Malan V, et al. (2007) Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction. Am J Hum Genet 80: 988-993. doi:10.1086/515582. PubMed: 17436254.
8. Brockschmidt A, Todt U, Ryu S, Hoischen A, Landwehr C, et al. (2007) Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4. Hum Mol Genet 16: 1488-1494. doi:10.1093/hmg/ddm099. PubMed: 17478476.
9. Peippo M, Ignatius J, (2012) Pitt-Hopkins Syndrome. Mol Syndromol 2: 171-180. PubMed: 22670138.
10. Sepp M, Pruunsild P, Timmusk T, (2012) Pitt-Hopkins syndrome-associated mutations in TCF4 lead to variable impairment of the transcription factor function ranging from hypomorphic to dominant-negative effects. Hum Mol Genet 21: 2873-2888. doi:10.1093/hmg/dds112. PubMed: 22460224.
11. Forrest M, Chapman RM, Doyle AM, Tinsley CL, Waite A, et al. (2012) Functional analysis of TCF4 missense mutations that cause Pitt-Hopkins syndrome. Hum Mutat 33: 1676-1686. doi:10.1002/humu.22160. PubMed: 22777675.
12. de Pontual L, Mathieu Y, Golzio C, Rio M, Malan V, et al. (2009) Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome. Hum Mutat 30: 669-676. doi:10.1002/humu.20935. PubMed: 19235238.
13. Talkowski ME, Rosenfeld JA, Blumenthal I, Pillalamarri V, Chiang C, et al. (2012) Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell 149: 525-537. doi:10.1016/j.cell.2012.03.028. PubMed: 22521361.
14. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, et al. (2009) Common variants conferring risk of schizophrenia. Nature 460: 744-747. PubMed: 19571808.
15. Blake DJ, Forrest M, Chapman RM, Tinsley CL, O'Donovan MC, et al. (2010) TCF4, schizophrenia, and Pitt-Hopkins Syndrome. Schizophr Bull 36: 443-447. doi:10.1093/schbul/sbq035. PubMed: 20421335.
16. Zhu X, Gu H, Liu Z, Xu Z, Chen X, et al. (2013) Associations between TCF4 gene polymorphism and cognitive functions in schizophrenia patients and healthy controls. Neuropsychopharmacology 38: 683-689. doi:10.1038/npp.2012.234. PubMed: 23249814.
17. Quednow BB, Ettinger U, Mössner R, Rujescu D, Giegling I, et al. (2011) The schizophrenia risk allele C of the TCF4 rs9960767 polymorphism disrupts sensorimotor gating in schizophrenia spectrum and healthy volunteers. J Neurosci 31: 6684-6691. doi:10.1523/JNEUROSCI.0526-11.2011. PubMed: 21543597.
18. Wirgenes KV, Sønderby IE, Haukvik UK, Mattingsdal M, Tesli M, et al. (2012) TCF4 sequence variants and mRNA levels are associated with neurodevelopmental characteristics in psychotic disorders. Transl Psychiatry 2: e112. doi:10.1038/tp.2012.39. PubMed: 22832956.
19. Sepp M, Kannike K, Eesmaa A, Urb M, Timmusk T, (2011) Functional diversity of human basic helix-loop-helix transcription factor TCF4 isoforms generated by alternative 5' exon usage and splicing. PLOS ONE 6: e22138. doi:10.1371/journal.pone.0022138. PubMed: 21789225.
20. Liu Y, Ray SK, Yang XQ, Luntz-Leybman V, Chiu IM, (1998) A splice variant of E2-2 basic helix-loop-helix protein represses the brain-specific fibroblast growth factor 1 promoter through the binding to an imperfect E-box. J Biol Chem 273: 19269-19276. doi:10.1074/jbc.273.30.19269. PubMed: 9668116.
21. Massari ME, Murre C, (2000) Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol 20: 429-440. doi:10.1128/MCB.20.2.429-440.2000. PubMed: 10611221.
22. Brzózka MM, Radyushkin K, Wichert SP, Ehrenreich H, Rossner MJ, (2010) Cognitive and sensorimotor gating impairments in transgenic mice overexpressing the schizophrenia susceptibility gene Tcf4 in the brain. Biol Psychiatry 68: 33-40. doi:10.1016/j.biopsych.2010.04.026. PubMed: 20434134.
23. Bertrand N, Castro DS, Guillemot F, (2002) Proneural genes and the specification of neural cell types. Nat Rev Neurosci 3: 517-530. doi:10.1038/nrn874. PubMed: 12094208.
24. Powell LM, Jarman AP, (2008) Context dependence of proneural bHLH proteins. Curr Opin Genet Dev 18: 411-417. doi:10.1016/j.gde.2008.07.012. PubMed: 18722526.
25. Li S, Mattar P, Zinyk D, Singh K, Chaturvedi CP, et al. (2012) GSK3 temporally regulates neurogenin 2 proneural activity in the neocortex. J Neurosci 32: 7791-7805. doi:10.1523/JNEUROSCI.1309-12.2012. PubMed: 22674256.
26. Huang da W, Sherman BT, Lempicki RA, (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44-57. PubMed: 19131956.
27. Massagué J, (2012) TGFbeta signalling in context. Nat Rev Mol Cell Biol 13: 616-630. doi:10.1038/nrm3434. PubMed: 22992590.
28. Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA, (2009) Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest 119: 1438-1449. doi:10.1172/JCI38019. PubMed: 19487820.
29. Fernandez AM, Torres-Alemán I, (2012) The many faces of insulin-like peptide signalling in the brain. Nat Rev Neurosci 13: 225-239. doi:10.1038/nrn3209. PubMed: 22430016.
30. Gutierrez H, Davies AM, (2011) Regulation of neural process growth, elaboration and structural plasticity by NF-kappaB. Trends Neurosci 34: 316-325. doi:10.1016/j.tins.2011.03.001. PubMed: 21459462.
31. Qin ZH, Tao LY, Chen X, (2007) Dual roles of NF-kappaB in cell survival and implications of NF-kappaB inhibitors in neuroprotective therapy. Acta Pharmacol Sin 28: 1859-1872. doi:10.1111/j.1745-7254.2007.00741.x. PubMed: 18031598.
32. Hyman BT, Yuan J, (2012) Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology. Nat Rev Neurosci 13: 395-406. doi:10.1038/nrn3228. PubMed: 22595785.
33. Bond AM, Bhalala OG, Kessler JA, (2012) The dynamic role of bone morphogenetic proteins in neural stem cell fate and maturation. Dev Neurobiol 72: 1068-1084. doi:10.1002/dneu.22022. PubMed: 22489086.
34. Panchision DM, Pickel JM, Studer L, Lee SH, Turner PA, et al. (2001) Sequential actions of BMP receptors control neural precursor cell production and fate. Genes Dev 15: 2094-2110. doi:10.1101/gad.894701. PubMed: 11511541.
35. Segklia A, Seuntjens E, Elkouris M, Tsalavos S, Stappers E, et al. (2012) Bmp7 regulates the survival, proliferation, and neurogenic properties of neural progenitor cells during corticogenesis in the mouse. PLOS ONE 7: e34088. doi:10.1371/journal.pone.0034088. PubMed: 22461901.
36. Nieto MA, (2011) The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu Rev Cell Dev Biol 27: 347-376. doi:10.1146/annurev-cellbio-092910-154036. PubMed: 21740232.
37. Cobaleda C, Pérez-Caro M, Vicente-Dueñas C, Sánchez-García I, (2007) Function of the zinc-finger transcription factor SNAI2 in cancer and development. Annu Rev Genet 41: 41-61. doi:10.1146/annurev.genet.41.110306.130146. PubMed: 17550342.
38. Wu Y, Sato F, Yamada T, Bhawal UK, Kawamoto T, et al. (2012) The BHLH transcription factor DEC1 plays an important role in the epithelial-mesenchymal transition of pancreatic cancer. Int J Oncol 41: 1337-1346. PubMed: 22825629.
39. Sobrado VR, Moreno-Bueno G, Cubillo E, Holt LJ, Nieto MA, et al. (2009) The class I bHLH factors E2-2A and E2-2B regulate EMT. J Cell Sci 122: 1014-1024. doi:10.1242/jcs.028241. PubMed: 19295128.
40. Moreno-Bueno G, Cubillo E, Sarrió D, Peinado H, Rodríguez-Pinilla SM, et al. (2006) Genetic profiling of epithelial cells expressing E-cadherin repressors reveals a distinct role for Snail, Slug, and E47 factors in epithelial-mesenchymal transition. Cancer Res 66: 9543-9556. doi:10.1158/0008-5472.CAN-06-0479. PubMed: 17018611.
41. Bolós V, Peinado H, Pérez-Moreno MA, Fraga MF, Esteller M, et al. (2003) The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci 116: 499-511. doi:10.1242/jcs.00224. PubMed: 12508111.
42. Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, et al. (2011) A critical role for IGF-II in memory consolidation and enhancement. Nature 469: 491-497. doi:10.1038/nature09667. PubMed: 21270887.
43. Bracko O, Singer T, Aigner S, Knobloch M, Winner B, et al. (2012) Gene expression profiling of neural stem cells and their neuronal progeny reveals IGF2 as a regulator of adult hippocampal neurogenesis. J Neurosci 32: 3376-3387. doi:10.1523/JNEUROSCI.4248-11.2012. PubMed: 22399759.
44. Schmeisser MJ, Baumann B, Johannsen S, Vindedal GF, Jensen V, et al. (2012) IkappaB kinase/nuclear factor kappa B-dependent insulin-like growth factor 2 (Igf2) expression regulates synapse formation and spine maturation via Igf2 receptor signaling. J Neurosci 32: 5688-5703. doi:10.1523/JNEUROSCI.0111-12.2012. PubMed: 22514330.
45. Van Balkom ID, Vuijk PJ, Franssens M, Hoek HW, Hennekam RC, (2012) Development, cognition, and behaviour in Pitt-Hopkins syndrome. Dev Med Child Neurol 54: 925-931. doi:10.1111/j.1469-8749.2012.04339.x. PubMed: 22712893.
46. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, et al. (2009) Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A 106: 2029-2034. doi:10.1073/pnas.0812394106. PubMed: 19208815.
47. Bhattacharya A, Kaphzan H, Alvarez-Dieppa AC, Murphy JP, Pierre P, et al. (2012) Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron 76: 325-337. doi:10.1016/j.neuron.2012.07.022. PubMed: 23083736.
48. Armani R, Archer H, Clarke A, Vasudevan P, Zweier C, et al. (2012) Transcription factor 4 and myocyte enhancer factor 2C mutations are not common causes of Rett syndrome. Am J Med Genet A 158A: 713-719. doi:10.1002/ajmg.a.34206. PubMed: 22383159.
49. Le Meur N, Holder-Espinasse M, Jaillard S, Goldenberg A, Joriot S, et al. (2010) MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations. J Med Genet 47: 22-29. doi:10.1136/jmg.2009.069732. PubMed: 19592390.
50. Zweier M, Rauch A, (2012) The MEF2C-Related and 5q14.3q15 Microdeletion Syndrome. Mol Syndromol 2: 164-170. PubMed: 22670137.
51. Remacle JE, Kraft H, Lerchner W, Wuytens G, Collart C, et al. (1999) New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites. EMBO J 18: 5073-5084. doi:10.1093/emboj/18.18.5073. PubMed: 10487759.
52. Molkentin JD, Olson EN, (1996) Combinatorial control of muscle development by basic helix-loop-helix and MADS-box transcription factors. Proc Natl Acad Sci U S A 93: 9366-9373. doi:10.1073/pnas.93.18.9366. PubMed: 8790335.
53. Esapa CT, Waite A, Locke M, Benson MA, Kraus M, et al. (2007) SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA. Hum Mol Genet 16: 327-342. PubMed: 17200151.
54. Waite A, De Rosa MC, Brancaccio A, Blake DJ, (2011) A gain-of-glycosylation mutation associated with myoclonus-dystonia syndrome affects trafficking and processing of mouse epsilon-sarcoglycan in the late secretory pathway. Hum Mutat 32: 1246-1258. doi:10.1002/humu.21561. PubMed: 21796726.
55. Locke M, Tinsley CL, Benson MA, Blake DJ, (2009) TRIM32 is an E3 ubiquitin ligase for dysbindin. Hum Mol Genet 18: 2344-2358. doi:10.1093/hmg/ddp167. PubMed: 19349376.
56. Edgar R, Domrachev M, Lash AE, (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207-210. doi:10.1093/nar/30.1.207. PubMed: 11752295.
57. Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M, (2004) The KEGG resource for deciphering the genome. Nucleic Acids Res 32: D277-D280. doi:10.1093/nar/gkh063. PubMed: 14681412.
58. Hoffmann R, (2008) A wiki for the life sciences where authorship matters. Nat Genet 40: 1047-1051. doi:10.1038/ng.f.217. PubMed: 18728691.
59. Mabb AM, Judson MC, Zylka MJ, Philpot BD, (2011) Angelman syndrome: insights into genomic imprinting and neurodevelopmental phenotypes. Trends Neurosci 34: 293-303. doi:10.1016/j.tins.2011.04.001. PubMed: 21592595.
60. Garavelli L, Mainardi PC, (2007) Mowat-Wilson syndrome. Orphanet J Rare Dis 2: 42. doi:10.1186/1750-1172-2-42. PubMed: 17958891.
61. Bhakar AL, Dölen G, Bear MF, (2012) The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci 35: 417-443. doi:10.1146/annurev-neuro-060909-153138. PubMed: 22483044.