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Article Dans Une Revue Developmental Biology Année : 2013

Sox10 and Itgb1 interaction in enteric neural crest cell migration

Résumé

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.

Dates et versions

hal-01712242 , version 1 (19-02-2018)

Identifiants

Citer

Yuli Watanabe, Florence Broders-Bondon, Viviane Baral, Perrine Paul-Gilloteaux, Veronique Pingault, et al.. Sox10 and Itgb1 interaction in enteric neural crest cell migration. Developmental Biology, 2013, 379 (1), pp.92 - 106. ⟨10.1016/j.ydbio.2013.04.013⟩. ⟨hal-01712242⟩
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