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

First Author  Wang X Year  2008
Journal  J Cell Biol Volume  183
Issue  1 Pages  37-48
PubMed ID  18824566 Mgi Jnum  J:143315
Mgi Id  MGI:3826689 Doi  10.1083/jcb.200804030
Citation  Wang X, et al. (2008) AP-2 factors act in concert with Notch to orchestrate terminal differentiation in skin epidermis. J Cell Biol 183(1):37-48
abstractText  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-2alpha and AP-2gamma, 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-2alpha/AP-2gamma 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.
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