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doi: 10.1242/10.1242/dev.00453

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Development 130, 2341-2353 (2003)
Copyright © 2003 The Company of Biologists Limited

Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130

Sergio Ruiz1, Carmen Segrelles1, Ana Bravo3, Mirentxu Santos1, Paloma Perez2, Hugo Leis1,2,3, Jose L. Jorcano1 and Jesús M. Paramio1,*

1 Program on Cell and Molecular Biology and Gene Therapy. CIEMAT, Avenue Complutense 22, E28040 Madrid, Spain
2 Instituto de Biomedicina de Valencia. Jaime Roig 11, 46010-Valencia, Spain
3 Department of Animal Pathology, Veterinary School, University of Santiago de Compostela, E27002 Lugo, Spain

* Author for correspondence (e-mail: jesusm.paramio{at}ciemat.es)

Accepted 26 February 2003

The functions of p107 and p130, members of the retinoblastoma family, include the control of cell cycle progression and differentiation in several tissues. Our previous studies suggested a role for p107 and p130 in keratinocyte differentiation in vitro. We now extend these data using knockout animal models. We found impaired terminal differentiation in the interfollicular keratinocytes of p107/p130-double-null mice epidermis. In addition, we observed a decreased number of hair follicles and a clear developmental delay in hair, whiskers and tooth germs. Skin grafts of p107/p130-deficient epidermis onto NOD/scid mice showed altered differentiation and hyperproliferation of the interfollicular keratinocytes, thus demonstrating that the absence of p107 and p130 results in the deficient control of differentiation in keratinocytes in a cell-autonomous manner. Besides normal hair formation, follicular cysts, misoriented and dysplastic follicles, together with aberrant hair cycling, were also observed in the p107/p130 skin transplants. Finally, the hair abnormalities in p107/p130-null skin were associated with altered Bmp4-dependent signaling including decreased {Delta}Np63 expression. These results indicate an essential role for p107 and p130 in the epithelial-mesenchimal interactions.

Key words: Mouse, Keratinocytes, p107, p130


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