Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation

Here we report on investigation of the role of the POU domain genes Skin-1a/i (Skn-1a/i/Epoc/Oct-11) and Testes-1 (Tst-1/Oct-6/SCIP) in epidermis where proliferating basal keratinocytes withdraw from the cell cycle, migrate suprabasally, and terminally differentiate to form a multilayered, stratifie...

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Published in:Genes & development 1997-07, Vol.11 (14), p.1873-1884
Main Authors: Andersen, B, Weinberg, W C, Rennekampff, O, McEvilly, R J, Bermingham, Jr, J R, Hooshmand, F, Vasilyev, V, Hansbrough, J F, Pittelkow, M R, Yuspa, S H, Rosenfeld, M G
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - genetics
Cells, Cultured
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Epidermal Cells
Epidermis - growth & development
Epidermis - metabolism
Genotype
Humans
Keratinocytes - cytology
Membrane Proteins - genetics
Mice
Mice, Knockout
Octamer Transcription Factor-6
POU Domain Factors
Repressor Proteins
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription Factors - physiology
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Summary:Here we report on investigation of the role of the POU domain genes Skin-1a/i (Skn-1a/i/Epoc/Oct-11) and Testes-1 (Tst-1/Oct-6/SCIP) in epidermis where proliferating basal keratinocytes withdraw from the cell cycle, migrate suprabasally, and terminally differentiate to form a multilayered, stratified epithelium. The expression of the Skn-1a/i and Tst-1 genes is linked to keratinocyte differentiation in vivo and in vitro, whereas the ubiquitous POU domain factor Oct-1 is expressed highly in both proliferating and post-mitotic keratinocytes. Analysis of Skn-1a/i gene-deleted mice reveals that the Skn-1a/i gene modulates the pattern of expression of the terminal differentiation marker loricrin and inhibits expression of genes encoding markers of the epidermal keratinocyte wounding response. Although epidermis from Tst-1 gene-deleted mice develops normally, epidermis from mice deleted for both Skn-1a/i and Tst-1 is hyperplastic and fails to suppress expression of K14 and Spr-1 in suprabasal cells when transplanted onto athymic mice. This suggests that Skn-1a/i and Tst-1 serve redundant functions in epidermis. Therefore, at least two POU domain genes, Skn-1a/i and Tst-1, serve both distinct and overlapping functions to regulate differentiation of epidermal keratinocytes during normal development and wound healing.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.11.14.1873