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Development. 2013 Sep;140(18):3809-18. doi: 10.1242/dev.097477. Epub 2013 Aug 14.

Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18.

Author information

  • 1Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505, Houston, TX 77030, USA.

Abstract

Hair follicles cyclically degenerate and regenerate throughout adult life and require regular stem cell activation to drive the cycle. In the resting phase of the hair cycle, hair follicle stem cells are maintained in a quiescent state until they receive signals to proliferate. We found that the forkhead transcription factor Foxp1 is crucial for maintaining the quiescence of hair follicle stem cells. Loss of Foxp1 in skin epithelial cells leads to precocious stem cell activation, resulting in drastic shortening of the quiescent phase of the hair cycle. Conversely, overexpression of Foxp1 in keratinocytes prevents cell proliferation by promoting cell cycle arrest. Finally, through both gain- and loss-of-function studies, we identify fibroblast growth factor 18 (Fgf18) as the key downstream target of Foxp1. We show that exogenously supplied FGF18 can prevent the hair follicle stem cells of Foxp1 null mice from being prematurely activated. As Fgf18 controls the length of the quiescent phase and is a key downstream target of Foxp1, our data strongly suggest that Foxp1 regulates the quiescent stem cell state in the hair follicle stem cell niche by controlling Fgf18 expression.

KEYWORDS:

Fgf18; Foxp1; Mouse; Skin; Stem cells; hair follicle; p57KIP2

PMID:
23946441
[PubMed - indexed for MEDLINE]
PMCID:
PMC3754479
Free PMC Article
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