title: How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration.
abstract: Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.
authors.affiliation: Laboratoire Matière et Systèmes Complexes, Université Paris-Diderot/CNRS UMR 7057, 10 rue Alice Domon et Léonie Duquet, 75013 Paris, France.
authors.forename: N R
authors.initials: NR
authors.lastname: Chevalier
authors.affiliation: UMR144, CNRS-Institut Curie, 26, rue d'Ulm, 75248 Paris cedex 05, France.
authors.forename: E
authors.initials: E
authors.lastname: Gazguez
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, F-75005, France.|INSERM, U1050, Paris, F-75005, France.|CNRS, UMR 7241, Paris, F-75005, France.
authors.forename: L
authors.initials: L
authors.lastname: Bidault
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Guilbert
authors.affiliation: Laboratoire Matière et Systèmes Complexes, Université Paris-Diderot/CNRS UMR 7057, 10 rue Alice Domon et Léonie Duquet, 75013 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Vias
authors.affiliation: Laboratoire Matière et Systèmes Complexes, Université Paris-Diderot/CNRS UMR 7057, 10 rue Alice Domon et Léonie Duquet, 75013 Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Vian
authors.affiliation: INSERM U955, Equipe 11, F-94000 Créteil, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, F-75005, France.|INSERM, U1050, Paris, F-75005, France.|CNRS, UMR 7241, Paris, F-75005, France.
authors.forename: L
authors.initials: L
authors.lastname: Muller
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, F-75005, France.|INSERM, U1050, Paris, F-75005, France.|CNRS, UMR 7241, Paris, F-75005, France.
authors.forename: S
authors.initials: S
authors.lastname: Germain
authors.affiliation: INSERM U955, Equipe 11, F-94000 Créteil, France.
authors.forename: N
authors.initials: N
authors.lastname: Bondurand
authors.affiliation: UMR144, CNRS-Institut Curie, 26, rue d'Ulm, 75248 Paris cedex 05, France.
authors.forename: S
authors.initials: S
authors.lastname: Dufour
authors.affiliation: Laboratoire Matière et Systèmes Complexes, Université Paris-Diderot/CNRS UMR 7057, 10 rue Alice Domon et Léonie Duquet, 75013 Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Fleury
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002642:Chick Embryo; D017364:Collagenases / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology* / Q000648:ultrastructure*; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D041981:Gastrointestinal Tract / Q000196:embryology* / Q000648:ultrastructure*; D051379:Mice; D018625:Microscopy, Atomic Force; D009432:Neural Crest / Q000196:embryology* / Q000648:ultrastructure*
chemical_list: D017364:Collagenases