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(American Journal of Pathology. 2004;165:729-740.)
© 2004 American Society for Investigative Pathology

Bone Morphogenetic Protein Signaling Regulates Postnatal Hair Follicle Differentiation and Cycling

Udayan Guha^*, Lars Mecklenburg, Pamela Cowin, Lixin Kan^¶, W. Michael O’Guin, Dolores D’Vizio^||, Richard G. Pestell^||, Ralf Paus and John A. Kessler^¶

From the Department of Dermatology, University of Hamburg, Hamburg, Germany; Veterinary Dermatopathology Consultant, Hamburg, Germany; the Department of Neuroscience,^* Albert Einstein College of Medicine, Bronx, New York; the Department of Oncology,|| Georgetown University Medical Center, Washington, DC; The Ronald O. Perelman Department of Dermatology and Department of Cell Biology, New York University Medical Center, New York, New York; and the Department of Neurology, ^¶ Northwestern University Medical School, Chicago, Illinois

Hair follicle morphogenesis and cycling were examined in transgenic mice that overexpress the bone morphogenetic protein (BMP) inhibitor Noggin under the control of the neuron-specific enolase promoter. The Noggin transgene was misexpressed in the proximal portion of the hair follicle, primarily the matrix cells, apart from the usual expression in neurons. Transgene expression appeared only after induction of both the primary (tylotrich) and secondary (nontylotrich) pelage hair follicles had already occurred, thus allowing examination of the role of BMP signaling in follicles that had been induced normally in the presence of BMPs. The overexpression of Noggin in these animals resulted in a dramatic loss of hair postnatally. There was an apparently normal, but shortened period of postnatal hair follicle morphogenesis, followed by premature initiation of hair follicle cycling via entry into the first catagen transformation. This resulted in a complete loss of hair shafts from the nontylotrich hair follicles in these mice while the tylotrich hair follicles were normal. The onset of anagen of the first postnatal hair follicle cycle was also accelerated in the transgenic mice. Our results show that BMP signaling is specifically required for proper proliferation and differentiation during late morphogenesis of nontylotrich hair follicles and that inhibition of this signaling pathway may be one of the triggers for the onset of catagen when the follicles are in anagen and the onset of anagen when the follicles are in telogen. Ectopic sebocyte differentiation was another hallmark of the phenotype of these transgenic mice suggesting that BMP signaling may be an important determinant of lineage selection by common progenitor cells in the skin. BMPs likely promote a hair follicle-type differentiation pathway of keratinocytes while suppressing the sebaceous differentiation pathway of skin epithelium.

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