Key role of p63 in BMP-4-Induced Epidermal Commitment of Embryonic Stem Cells

Abstract

In vivo studies, transgenic and knock-out mice have demonstrated that p63 isoforms play pivotal roles in ectodermal and epidermal development but their respective function remains highly controversial. Since embryonic stem (ES) cells can be differentiated into many cell types, they represent an effective tool to recapitulate in vitro the main steps of embryonic development. We recently reported the efficient derivation of ectodermal and epidermal cells from murine ES cells and 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. DeltaNp63 is not required for ectodermal fate but enhances ES-derived ectodermal cell proliferation and epidermal commitment. This unique cellular model should further provide a powerful tool for identifying the molecular mechanisms controlling normal skin development and in p63-ectodermal dysplasia human congenital pathologies.

Location of transient ectodermal progenitor potential in mouse development

“…1G). Epidermal markers, the cytokeratins Krt8 (K8) and Krt18 (K18), were previously reported to be expressed in the single-layer ectodermal cells from E8.5 (Aberdam et al, 2007b). However, our data show that K8 and K18 expression is detectable in the anterior side as early as E7.5 (Fig.…”

A Pure Population of Ectodermal Cells Derived from Human Embryonic Stem Cells

“…We recently demonstrated that the exogenous expression of ⌬Np63 is necessary to differentiate murine K8/K18 ϩ ectodermal cells into K5/K14 ϩ keratinocytes [17]. Accordingly, IT1 cells, transduced with a lentivirus expressing ⌬Np63, became K14-positive cells (Fig.…”

p63 in epithelial development

“…However, TAp63 isoforms have not been detected by in situ hybridization or immunoblot; thus TAp63 protein levels appear to be barey detectable [13,20]. Studies in ES-derived cells shows that BMP-4 treatment, leading to the ectodermal fate, induces Np63, while exogenous expression of the Np63 isoform in ES-derived ectodermal cells efficiently leads to their differentiation into keratinocytes [21].…”