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

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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
Volume24
Issue number13
DOIs
Publication statusPublished - 2004

Cite this

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title = "The transcription factors c-rel and RelA control epidermal development and homeostasis in embryonic and adult skin via distinct mechanisms",
abstract = "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.",
author = "Raffi Gugasyan and Voss, {Anne K} and George Varigos and Tim Thomas and Grumont, {Raelene Joy} and Pritinder Kaur and George Grigoriadis and Gerondakis, {Steven Demetrious}",
year = "2004",
doi = "10.1128/MCB.24.13.5733-5745.2004",
language = "English",
volume = "24",
pages = "5733 -- 5745",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "Am Soc Microbiol",
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}

The transcription factors c-rel and RelA control epidermal development and homeostasis in embryonic and adult skin via distinct mechanisms. / Gugasyan, Raffi; Voss, Anne K; Varigos, George; Thomas, Tim; Grumont, Raelene Joy; Kaur, Pritinder; Grigoriadis, George; Gerondakis, Steven Demetrious.

In: Molecular and Cellular Biology, Vol. 24, No. 13, 2004, p. 5733 - 5745.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The transcription factors c-rel and RelA control epidermal development and homeostasis in embryonic and adult skin via distinct mechanisms

AU - Gugasyan, Raffi

AU - Voss, Anne K

AU - Varigos, George

AU - Thomas, Tim

AU - Grumont, Raelene Joy

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AU - Grigoriadis, George

AU - Gerondakis, Steven Demetrious

PY - 2004

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N2 - 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.

AB - 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.

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