title: Embryonic stem cells as a cellular model for neuroectodermal commitment and skin formation.
abstract: Embryonic stem (ES) cells can be differentiated into many cell types in vitro, thus providing a potential unlimited supply of cells for cognitive in vitro studies and cell-based therapy. We recently reported the efficient derivation of ectodermal and epidermal cells from murine ES cells. These differentiated ES cells were able to form, in culture, a multilayered epidermis coupled with an underlying dermal compartment, similar to native skin. We clarified the function of BMP-4 in the binary neuroectodermal choice by stimulating sox-1(+) neural precursors to undergo specific apoptosis while inducing epidermal differentiation through DeltaNp63 gene activation. We further demonstrated that DeltaNp63 enhances ES-derived ectodermal cell proliferation and is necessary for epidermal commitment. This unique cellular model further provides a powerful tool for identifying the molecular mechanisms controlling normal skin development and for investigating p63-ectodermal dysplasia human congenital pathologies.
authors.affiliation: INSERM, U634, faculté de médecine, 28, av. de Valombrose, 06107 Nice cedex 2, France. aberdam@unice.fr
authors.forename: Daniel
authors.initials: D
authors.lastname: Aberdam
authors.forename: Karen
authors.initials: K
authors.lastname: Gambaro
authors.forename: Alain
authors.initials: A
authors.lastname: Medawar
authors.forename: Edith
authors.initials: E
authors.lastname: Aberdam
authors.forename: Philippe
authors.initials: P
authors.lastname: Rostagno
authors.forename: Stéphanie
authors.initials: S
authors.lastname: de la Forest Divonne
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rouleau
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D012867:Skin / Q000166:cytology* / Q000196:embryology*
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C081876:CKAP4 protein, human; D008565:Membrane Proteins