NDLI: Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis

Content Provider	PubMed Central
Author	Lacroix, Matthieu Julie, Caramel Perrine, Goguet-rubio Linares, Laetitia K. Estrach, Soline Hatchi, Elodie Rodier, Geneviève Lledo, Gwendaline Bettignies, Carine De Thépot, Amélie Céline, Deraison Karim, Chébli Hovnanian, Alain Hainaut, Pierre Dubus, Pierre Sardet, Claude Cam, Laurent Le
Abstract	A growing body of evidence suggests that the multifunctional protein E4F1 is involved in signaling pathways that play essential roles during normal development and tumorigenesis. We generated E4F1 conditional knockout mice to address E4F1 functions in vivo in newborn and adult skin. E4F1 inactivation in the entire skin or in the basal compartment of the epidermis induces skin homeostasis defects, as evidenced by transient hyperplasia in the interfollicular epithelium and alteration of keratinocyte differentiation, followed by loss of cellularity in the epidermis and severe skin ulcerations. E4F1 depletion alters clonogenic activity of epidermal stem cells (ESCs) ex vivo and ends in exhaustion of the ESC pool in vivo, indicating that the lesions observed in the E4F1 mutant skin result, at least in part, from cell-autonomous alterations in ESC maintenance. The clonogenic potential of E4F1 KO ESCs is rescued by Bmi1 overexpression or by Ink4a/Arf or p53 depletion. Skin phenotype of E4F1 KO mice is also delayed in animals with Ink4a/Arf and E4F1 compound gene deficiencies. Our data identify a regulatory axis essential for ESC-dependent skin homeostasis implicating E4F1 and the Bmi1–Arf–p53 pathway.
Related Links	http://dx.doi.org/10.1073/pnas.1010167107
Ending Page	21081
Page Count	6
Starting Page	21076
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	49
Volume Number	107
Language	English
Publisher	National Academy of Sciences
Publisher Date	2010-12-07
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Correction for Lacroix et al., Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis

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