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Publication : Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch.

First Author  Richardson RJ Year  2006
Journal  Nat Genet Volume  38
Issue  11 Pages  1329-34
PubMed ID  17041603 Mgi Jnum  J:116077
Mgi Id  MGI:3692825 Doi  10.1038/ng1894
Citation  Richardson RJ, et al. (2006) Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch. Nat Genet 38(11):1329-34
abstractText  The epidermis is a highly organized structure, the integrity of which is central to the protection of an organism. Development and subsequent maintenance of this tissue depends critically on the intricate balance between proliferation and differentiation of a resident stem cell population; however, the signals controlling the proliferation-differentiation switch in vivo remain elusive. Here, we show that mice carrying a homozygous missense mutation in interferon regulatory factor 6 (Irf6), the homolog of the gene mutated in the human congenital disorders Van der Woude syndrome and popliteal pterygium syndrome, have a hyperproliferative epidermis that fails to undergo terminal differentiation, resulting in soft tissue fusions. We further demonstrate that mice that are compound heterozygotes for mutations in Irf6 and the gene encoding the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show similar defects of keratinizing epithelia. Our results indicate that Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch and that Irf6 and Sfn interact genetically in this process.
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