title: Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development.
abstract: The requirement for SOX10 and endothelin-3/EDNRB signalling pathway during enteric nervous system (ENS) and melanocyte development, as well as their alterations in Waardenburg-Hirschsprung disease (hypopigmentation, deafness and absence of enteric ganglia) are well established. Here, we analysed the genetic interactions between these genes during ENS and melanocyte development. Through phenotype analysis of Sox10;Ednrb and Sox10;Edn3 double mutants, we show that a coordinate and balanced interaction between these molecules is required for normal ENS and melanocyte development. Indeed, double mutants present with a severe increase in white spotting, absence of melanocytes within the inner ear, and in the stria vascularis in particular, and more severe ENS defects. Moreover, we show that partial loss of Ednrb in Sox10 heterozygous mice impairs colonisation of the gut by enteric crest cells at all stages observed. However, compared to single mutants, we detected no apoptosis, cell proliferation or overall neuronal or glial differentiation defects in neural crest cells within the stomach of double mutants, but apoptosis was increased in vagal neural crest cells outside of the gut. These data will contribute to the understanding of the molecular basis of ENS, pigmentation and hearing defects observed in mouse mutants and patients carrying SOX10, EDN3 and EDNRB mutations.
authors.affiliation: INSERM, U654, Bases moléculaires et cellulaires des maladies génétiques, Hôpital Henri Mondor, Creteil, F-94000, France; Université Paris 12, Faculté de Médecine, IFR10, Créteil, F-94000, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Stanchina
authors.forename: Viviane
authors.initials: V
authors.lastname: Baral
authors.forename: Fabienne
authors.initials: F
authors.lastname: Robert
authors.forename: Veronique
authors.initials: V
authors.lastname: Pingault
authors.forename: Nicole
authors.initials: N
authors.lastname: Lemort
authors.forename: Vassilis
authors.initials: V
authors.lastname: Pachnis
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Nadege
authors.initials: N
authors.lastname: Bondurand
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D007758:Ear, Inner / Q000473:pathology; D019334:Endothelin-3 / Q000235:genetics / Q000378:metabolism*; D017615:Enteric Nervous System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006200:Hair Color / Q000235:genetics; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D008544:Melanocytes / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009026:Mortality; D009432:Neural Crest / Q000473:pathology; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism*; D055757:SOXE Transcription Factors; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D019334:Endothelin-3; D006609:High Mobility Group Proteins; D044023:Receptor, Endothelin B; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D014157:Transcription Factors