Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 5733 - 5745 |
| Number of pages | 13 |
| Journal | Molecular and Cellular Biology |
| Volume | 24 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - 2004 |
Cite this
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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 journal › Article › Research › peer-review
TY - JOUR
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
AU - Kaur, Pritinder
AU - Grigoriadis, George
AU - Gerondakis, Steven Demetrious
PY - 2004
Y1 - 2004
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.
UR - http://mcb.asm.org.ezproxy.lib.monash.edu.au/content/24/13/5733
U2 - 10.1128/MCB.24.13.5733-5745.2004
DO - 10.1128/MCB.24.13.5733-5745.2004
M3 - Article
VL - 24
SP - 5733
EP - 5745
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 13
ER -