Wnt signaling induces differentiation of progenitor cells in organotypic keratinocyte cultures.
BACKGROUND
Interfollicular skin develops normally only when the activity of the progenitor cells in the basal layer is counterbalanced by the exit of cells into the suprabasal layers, where they differentiate and cornify to establish barrier function. Distinct stem and progenitor compartments have been demonstrated in hair follicles and sebaceous glands, but there are few data to describe the control of interfollicular progenitor cell activity. Wnt signaling has been shown to be an important growth-inducer of stem cell compartments in skin and many other tissues.


RESULTS
Here, we test the effect of ectopic Wnt1 expression on the behavior of interfollicular progenitor cells in an organotypic culture model, and find that Wnt1 signaling inhibits their growth and promotes terminal differentiation.


CONCLUSIONS
These results are consistent with the phenotypes reported for transgenic mice engineered to have gain or loss of function of Wnt signaling in skin, which would recommend our culture model as an accurate one for molecular analysis. Since it is known that canonical ligands are expressed in skin, it is likely that this pathway normally regulates the balance of growth and differentiation, and suggests it could be important to pathogenesis.
Slavik
Marni A
MA
McArdle Lab for Cancer Research, University of Wisconsin Medical School-Madison, Madison, Wisconsin, USA. marnislavik@yahoo.com <marnislavik@yahoo.com>
Allen-Hoffmann
B Lynn
BL
Liu
Bob Y
BY
Alexander
Caroline M
CM
D000818:Animals; D002454:Cell Differentiation; D049108:Cell Enlargement; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D041681:NIH 3T3 Cells; D009924:Organ Culture Techniques; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D014162:Transfection; D051155:Wnt1 Protein / Q000502:physiology*
C495247:WNT1 protein, human; D051155:Wnt1 Protein