title: Enteric neural crest cells regulate vertebrate stomach patterning and differentiation.
abstract: In vertebrates, the digestive tract develops from a uniform structure where reciprocal epithelial-mesenchymal interactions pattern this complex organ into regions with specific morphologies and functions. Concomitant with these early patterning events, the primitive GI tract is colonized by the vagal enteric neural crest cells (vENCCs), a population of cells that will give rise to the enteric nervous system (ENS), the intrinsic innervation of the GI tract. The influence of vENCCs on early patterning and differentiation of the GI tract has never been evaluated. In this study, we report that a crucial number of vENCCs is required for proper chick stomach development, patterning and differentiation. We show that reducing the number of vENCCs by performing vENCC ablations induces sustained activation of the BMP and Notch pathways in the stomach mesenchyme and impairs smooth muscle development. A reduction in vENCCs also leads to the transdifferentiation of the stomach into a stomach-intestinal mixed phenotype. In addition, sustained Notch signaling activity in the stomach mesenchyme phenocopies the defects observed in vENCC-ablated stomachs, indicating that inhibition of the Notch signaling pathway is essential for stomach patterning and differentiation. Finally, we report that a crucial number of vENCCs is also required for maintenance of stomach identity and differentiation through inhibition of the Notch signaling pathway. Altogether, our data reveal that, through the regulation of mesenchyme identity, vENCCs act as a new mediator in the mesenchymal-epithelial interactions that control stomach development.
authors.affiliation: INSERM U1046, Université Montpellier 1, Université Montpellier 2, Montpellier 34295, France sandrine.faure@inserm.fr pascal.de-santa-barbara@inserm.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faure
authors.affiliation: INSERM U1046, Université Montpellier 1, Université Montpellier 2, Montpellier 34295, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: McKey
authors.affiliation: INSERM U1046, Université Montpellier 1, Université Montpellier 2, Montpellier 34295, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Sagnol
authors.affiliation: INSERM U1046, Université Montpellier 1, Université Montpellier 2, Montpellier 34295, France sandrine.faure@inserm.fr pascal.de-santa-barbara@inserm.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: de Santa Barbara
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002642:Chick Embryo; D017615:Enteric Nervous System / Q000196:embryology*; D005455:Fluorescent Antibody Technique; D017403:In Situ Hybridization; D009024:Morphogenesis / Q000502:physiology*; D009130:Muscle, Smooth / Q000196:embryology; D009432:Neural Crest / Q000196:embryology*; D009924:Organ Culture Techniques; D051880:Receptors, Notch / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013270:Stomach / Q000196:embryology* / Q000294:innervation
chemical_list: D019485:Bone Morphogenetic Proteins; D051880:Receptors, Notch
keywords: Chick; Enteric neural crest cells; Gut development; Mesenchymal-epithelial interactions; Notch pathway; Smooth muscle differentiation