Embryonic stem cells as a cellular model for neuroectodermal commitment and skin formation.
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.
Aberdam
Daniel
D
INSERM, U634, faculté de médecine, 28, av. de Valombrose, 06107 Nice cedex 2, France. aberdam@unice.fr
Gambaro
Karen
K
Medawar
Alain
A
Aberdam
Edith
E
Rostagno
Philippe
P
de la Forest Divonne
Stéphanie
S
Rouleau
Matthieu
M
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*
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C081876:CKAP4 protein, human; D008565:Membrane Proteins