title: Genetic interaction between Sox10 and Zfhx1b during enteric nervous system development.
abstract: The involvement of SOX10 and ZFHX1B in Waardenburg-Hirschsprung disease (hypopigmentation, deafness, and absence of enteric ganglia) and Mowat-Wilson syndrome (mental retardation, facial dysmorphy and variable congenital malformations including Hirschsprung disease) respectively, highlighted the importance of both transcription factors during enteric nervous system (ENS) development. The expression and function of SOX10 are now well established, but those of ZFHX1B remain elusive. Here we describe the expression profile of Zfhx1b and its genetic interactions with Sox10 during mouse ENS development. Through phenotype analysis of Sox10;Zfhx1b double mutants, we show that a coordinated and balanced interaction between these two genes is required for normal ENS development. Double mutants present with more severe ENS defects due to decreased proliferation of enteric progenitors and increased neuronal differentiation from E11.5 onwards. Thus, joint activity between these two transcription factors is crucial for proper ENS development and our results contribute to the understanding of the molecular basis of ENS defects observed both in mutant mouse models and in patients carrying SOX10 and ZFHX1B mutations.
authors.affiliation: INSERM U955, IMRB, Equipe 11, Creteil, F-94010, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Stanchina
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Putte
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Danny
authors.initials: D
authors.lastname: Huylebroeck
authors.forename: Nadege
authors.initials: N
authors.lastname: Bondurand
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D004622:Embryo, Mammalian / Q000378:metabolism; D017615:Enteric Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006627:Hirschsprung Disease / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009154:Mutation; D009457:Neuroglia / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2