title: Sox10 and Itgb1 interaction in enteric neural crest cell migration.
abstract: SOX10 involvement in syndromic form of Hirschsprung disease (intestinal aganglionosis, HSCR) in humans as well as developmental defects in animal models highlight the importance of this transcription factor in control of the pool of enteric progenitors and their differentiation. Here, we characterized the role of SOX10 in cell migration and its interactions with β1-integrins. To this end, we crossed the Sox10(lacZ/+) mice with the conditional Ht-PA::Cre; beta1(neo/+) and beta1(fl/fl) mice and compared the phenotype of embryos of different genotypes during enteric nervous system (ENS) development. The Sox10(lacZ/+); Ht-PA::Cre; beta1(neo/fl) double mutant embryos presented with increased intestinal aganglionosis length and more severe neuronal network disorganization compared to single mutants. These defects, detected by E11.5, are not compensated after birth, showing that a coordinated and balanced interaction between these two genes is required for normal ENS development. Use of video-microscopy revealed that defects observed result from reduced migration speed and altered directionality of enteric neural crest cells. Expression of β1-integrins upon SOX10 overexpression or in Sox10(lacZ/+) mice was also analyzed. The modulation of SOX10 expression altered β1-integrins, suggesting that SOX10 levels are critical for proper expression and function of this adhesion molecule. Together with previous studies, our results strongly indicate that SOX10 mediates ENCC adhesion and migration, and contribute to the understanding of the molecular and cellular basis of ENS defects observed both in mutant mouse models and in patients carrying SOX10 mutations.
authors.affiliation: INSERM U955, Equipe 11, F-94000 Créteil, France; Université Paris-Est, UMR_S955, UPEC, F-94000 Créteil, France.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Florence
authors.initials: F
authors.lastname: Broders-Bondon
authors.forename: Viviane
authors.initials: V
authors.lastname: Baral
authors.forename: Perrine
authors.initials: P
authors.lastname: Paul-Gilloteaux
authors.forename: Veronique
authors.initials: V
authors.lastname: Pingault
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dufour
authors.forename: Nadege
authors.initials: N
authors.lastname: Bondurand
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000378:metabolism; D017615:Enteric Nervous System / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D057895:Haploinsufficiency; D006627:Hirschsprung Disease / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D025941:Protein Interaction Mapping; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D019012:Integrin beta1; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse