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1477-9129141242014DecDevelopment (Cambridge, England)DevelopmentFezf2 promotes neuronal differentiation through localised activation of Wnt/β-catenin signalling during forebrain development.479448054794-80510.1242/dev.115691Brain regionalisation, neuronal subtype diversification and circuit connectivity are crucial events in the establishment of higher cognitive functions. Here we report the requirement for the transcriptional repressor Fezf2 for proper differentiation of neural progenitor cells during the development of the Xenopus forebrain. Depletion of Fezf2 induces apoptosis in postmitotic neural progenitors, with concomitant reduction in forebrain size and neuronal differentiation. Mechanistically, we found that Fezf2 stimulates neuronal differentiation by promoting Wnt/β-catenin signalling in the developing forebrain. In addition, we show that Fezf2 promotes activation of Wnt/β-catenin signalling by repressing the expression of two negative regulators of Wnt signalling, namely lhx2 and lhx9. Our findings suggest that Fezf2 plays an essential role in controlling when and where neuronal differentiation occurs within the developing forebrain and that it does so by promoting local Wnt/β-catenin signalling via a double-repressor model.© 2014. Published by The Company of Biologists Ltd.ZhangSiweiSThe Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.LiJingjingJThe Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.LeaRobertRThe Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.VleminckxKrisKDepartment for Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium.AmayaEnriqueEThe Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK enrique.amaya@manchester.ac.uk.eng097820/Z/11/ZWellcome TrustUnited KingdomWT082450MAWellcome TrustUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't
EnglandDevelopment87017440950-19910DNA Primers0Fezf2 protein, Xenopus0Transcription Factors0Xenopus Proteins0beta CateninEC 1.13.12.-LuciferasesIMAnalysis of VarianceAnimalsCell DifferentiationphysiologyChromatin ImmunoprecipitationDNA PrimersgeneticsImage Processing, Computer-AssistedIn Situ HybridizationIn Situ Nick-End LabelingLuciferasesMicroscopy, FluorescenceNeuronsphysiologyProsencephalonembryologyTranscription FactorsgeneticsmetabolismWnt Signaling PathwayphysiologyXenopusembryologyXenopus ProteinsgeneticsmetabolismZinc Fingersbeta CateninmetabolismFezf2Forebrain developmentWnt signallingXenopus2014124602014124602015256020141215ppublish25468942PMC429927810.1242/dev.115691141/24/4794Akkers R. C., van Heeringen S. J., Manak J. R., Green R. D., Stunnenberg H. G. and Veenstra G. J. C. (2010). ChIP-chip designs to interrogate the genome of Xenopus embryos for transcription factor binding and epigenetic regulation. 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