Nuclear factor I-C regulates TGF-{beta}-dependent hair follicle cycling.
Skin appendages such as teeth and hair share several common signaling pathways. The nuclear factor I C (NFI-C) transcription factor has been implicated in tooth development, but a potential role in hair growth had not been assessed. In this study we found that NFI-C regulates the onset of the hair growth cycle. NFI-C(-/-) mice were delayed in the transition from the telogen to anagen phase of the hair follicle cycle after either experimental depilation or spontaneous hair loss. Lack of NFI-C resulted in delayed induction of the sonic hedgehog, Wnt5a, and Lef1 gene expression, which are key regulators of the hair follicle growth initiation. NFI-C(-/-) mice also showed elevated levels of transforming growth factor β1 (TGF-β1), an inhibitor of keratinocyte proliferation, and of the cell cycle inhibitor p21 at telogen. Reduced expression of Ki67, a marker of cell proliferation, was noted at the onset of anagen, indicating impaired activation of the hair progenitor cells. These findings implicate NFI-C in the repression of TGF-β1 signaling during telogen stage, resulting in the delay of progenitor cell proliferation and hair follicle regeneration in NFI-C-deficient mice. Taken together with prior observations, these findings also designate NFI-C as a regulator of adult progenitor cell proliferation and of postnatal tissue growth or regeneration.
Plasari
Genta
G
Institute of Biotechnology, University of Lausanne, 1015 Lausanne, Switzerland.
Edelmann
Simone
S
Högger
Florence
F
Dusserre
Yves
Y
Mermod
Nicolas
N
Calabrese
Alessandra
A
D000818:Animals; D049109:Cell Proliferation; D006197:Hair / Q000502:physiology; D018859:Hair Follicle / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051839:NFI Transcription Factors / Q000737:chemistry*; D010641:Phenotype; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000096:biosynthesis; D000071818:Wnt-5a Protein
C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D051839:NFI Transcription Factors; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse