The transcription factors c-rel and RelA control epidermal development and homeostasis in embryonic and adult skin via distinct mechanisms

Raffi Gugasyan, Anne K Voss, George Varigos, Tim Thomas, Raelene Joy Grumont, Pritinder Kaur, George Grigoriadis, Steven Demetrious Gerondakis

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70 Citations (Scopus)


Determining the roles of Rel/NF-I?B transcription factors in mouse skin development with loss-of-function mutants has been limited by redundancy among these proteins and by embryonic lethality associated with the absence of RelA. Using mice lacking RelA and c-rel, which survive throughout embryogenesis on a tumor necrosis factor alpha (TNF-I?)-deficient background (rela -/- c-rel-/- tnfI?-/-), we show that c-rel and RelA are required for normal epidermal development. Although mutant fetuses fail to form tylotrich hair and have a thinner epidermis, mutant keratinocyte progenitors undergo terminal differentiation to form an outer cornified layer. Mutant basal keratinocytes are abnormally small, exhibit a delay in G 1 progression, and fail to form keratinocyte colonies in culture. In contrast to the reduced proliferation of mutant keratinocytes during embryogenesis, skin grafting experiments revealed that the mutant epidermis develops a TNF-I?-dependent hyperproliferative condition. Collectively, our findings indicate that RelA and c-rel control the development of the epidermis and associated appendages during embryogenesis and regulate epidermal homeostasis in a postnatal environment through the suppression of innate immune-mediated inflammation.
Original languageEnglish
Pages (from-to)5733 - 5745
Number of pages13
JournalMolecular and Cellular Biology
Issue number13
Publication statusPublished - 2004

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