Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development.
Bone morphogenetic protein (BMP) signaling is thought to perform multiple functions in the regulation of skin appendage morphogenesis and the postnatal growth of hair follicles. However, definitive genetic evidence for these roles has been lacking. Here, we show that Cre-mediated mutation of the gene encoding BMP receptor 1A in the surface epithelium and its derivatives causes arrest of tooth morphogenesis and lack of external hair. The hair shaft and hair follicle inner root sheath (IRS) fail to differentiate, and expression of the known transcriptional regulators of follicular differentiation Msx1, Msx2, Foxn1 and Gata3 is markedly downregulated or absent in mutant follicles. Lef1 expression is maintained, but nuclear beta-catenin is absent from the epithelium of severely affected mutant follicles, indicating that activation of the WNT pathway lies downstream of BMPR1A signaling in postnatal follicles. Mutant hair follicles fail to undergo programmed regression, and instead continue to proliferate, producing follicular cysts and matricomas. These results provide definitive genetic evidence that epithelial Bmpr1a is required for completion of tooth morphogenesis, and regulates terminal differentiation and proliferation in postnatal hair follicles.
Andl
Thomas
T
Department of Dermatology, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.
Ahn
Kyung
K
Kairo
Alladin
A
Chu
Emily Y
EY
Wine-Lee
Lara
L
Reddy
Seshamma T
ST
Croft
Nirvana J
NJ
Cebra-Thomas
Judith A
JA
Metzger
Daniel
D
Chambon
Pierre
P
Lyons
Karen M
KM
Mishina
Yuji
Y
Seykora
John T
JT
Crenshaw
E Bryan
EB
Millar
Sarah E
SE
D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I; D002454:Cell Differentiation; D002455:Cell Division; D004817:Epidermis / Q000196:embryology; D005260:Female; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development*; D017403:In Situ Hybridization; D019426:Integrases / Q000235:genetics; D007774:Lactation; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D010012:Osteogenesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics
D017978:Receptors, Growth Factor; D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; C045073:Cre recombinase; D019426:Integrases