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, 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.
Andersen
B
B
Department of Medicine, University of California, San Diego, La Jolla 92037-0648, USA.
Weinberg
W C
WC
Rennekampff
O
O
McEvilly
R J
RJ
Bermingham
J R
JR
Hooshmand
F
F
Vasilyev
V
V
Hansbrough
J F
JF
Pittelkow
M R
MR
Yuspa
S H
SH
Rosenfeld
M G
MG
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism; D005838:Genotype; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D050816:Octamer Transcription Factor-6; D050809:POU Domain Factors; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D050809:POU Domain Factors; C494178:POU3F1 protein, human; C494180:Pou3f1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C064554:loricrin; D050816:Octamer Transcription Factor-6