title: Dystroglycan is involved in skin morphogenesis downstream of the Notch signaling pathway.
abstract: Dystroglycan (Dg) is a transmembrane protein involved both in the assembly and maintenance of basement membrane structures essential for tissue morphogenesis, and the transmission of signals across the plasma membrane. We used a morpholino knockdown approach to investigate the function of Dg during Xenopus laevis skin morphogenesis. The loss of Dg disrupts epidermal differentiation by affecting the intercalation of multiciliated cells, deposition of laminin, and organization of fibronectin in the extracellular matrix (ECM). Depletion of Dg also affects cell-cell adhesion, as shown by the reduction of E-cadherin expression at the intercellular contacts, without affecting the distribution of β(1) integrins. This was associated with a decrease of cell proliferation, a disruption of multiciliated-cell intercalation, and the down-regulation of the transcription factor P63, a marker of differentiated epidermis. In addition, we demonstrated that inhibition or activation of the Notch pathway prevents and promotes transcription of X-dg. Our study showed for the first time in vivo that Dg, in addition to organizing laminin in the ECM, also acts as a key signaling component in the Notch pathway.
authors.affiliation: Laboratoire de Biologie du Développement, Université Pierre et Marie Curie, Sorbonne Universités, UMR CNRS 7622, 75252 Paris Cedex 05, France.
authors.forename: Cathy
authors.initials: C
authors.lastname: Sirour
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Valérie
authors.initials: V
authors.lastname: Bello
authors.forename: Nicolas
authors.initials: N
authors.lastname: Buisson
authors.forename: Thierry
authors.initials: T
authors.lastname: Darribère
authors.forename: Nicole
authors.initials: N
authors.lastname: Moreau
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000254:growth & development* / Q000378:metabolism; D004843:Epistasis, Genetic; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D020868:Gene Silencing; D019012:Integrin beta1 / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D007814:Larva / Q000166:cytology / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D054261:Neurulation; D010750:Phosphoproteins / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis / Q000254:growth & development* / Q000378:metabolism
chemical_list: D015820:Cadherins; D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin; C549535:NOTCH1 protein, Xenopus; D010750:Phosphoproteins; D051880:Receptors, Notch; C488640:TP63 protein, Xenopus; D015534:Trans-Activators; D029867:Xenopus Proteins; C121346:laminin 1; D049030:Dystroglycans