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AP-2 factors act in concert with Notch to orchestrate terminal differentiation in skin epidermis

¹ The Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065
² Department of Craniofacial Biology and Cell and Developmental Biology, University of Colorado Health Sciences Center, Aurora, CO 80045

Correspondence to Elaine Fuchs: fuchslb{at}rockefeller.edu

The mechanisms by which mammalian epidermal stem cells cease to proliferate and embark upon terminal differentiation are still poorly understood. By conditionally ablating two highly expressed transcription factors, AP-2 and AP-2, we unmasked functional redundancies and discovered an essential role for AP-2s in the process. In vivo and in vitro, AP-2 deficiency is accompanied by surprisingly minimal changes in basal gene expression but severely perturbed terminal differentiation and suppression of additional transcription factors and structural genes involved. In dissecting the underlying molecular pathways, we uncover parallel pathways involving AP-2 and Notch signaling, which converge to govern CCAAT/enhancer binding protein genes and orchestrate the transition from basal proliferation to suprabasal differentiation. Finally, we extend the striking similarities in compromising either Notch signaling or AP-2/AP-2 in developing skin to that in postnatal skin, where all hair follicles and sebaceous gland differentiation are also repressed and overt signs of premalignant conversion emerge.

© 2008 Wang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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