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Abnormal hair development and apparent follicular transformation to mammary gland in the absence of Hedgehog signaling

Journal article
Authors Amel Gritli Linde
Kristina Hallberg
Brian D Harfe
Azadeh Reyahi
Marie Kannius-Janson
Jeanette Nilsson
Martyn T. Cobourne
Paul T. Sharpe
Andrew P McMahon
Anders Linde
Published in Developmental Cell
Volume 12
Issue 1
Pages 99-112
Publication year 2007
Published at Institute of Odontology
Department of Cell and Molecular Biology
Pages 99-112
Language en
Links www.pubmedcentral.nih.gov/articlere...
Keywords Sonic hedgehog, Smoothened, cell signaling, epithelium, mesenchyme, stem cell
Subject categories Developmental Biology, Medical cell biology, Biochemistry, Cell and molecular biology, Morphology

Abstract

Here, we show that removing the Shh receptor Smoothened from the skin epithelium results in a seemingly contradictory constellation of phenotypes including cellular disorganization, altered proliferation, and loss of hair follicle (HF) progenitors. We provide evidence that the lack of Smoothened in the epithelium results in excess Shh levels in the mesenchyme. Thus, the observed defects can be attributed not only to decreased epithelial Shh signaling, but increased mesenchymal Shh signalling. The latter contributes to exuberant HF induction, while the former depletes the resulting follicular stem cell niches. Two additional, unanticipated epithelial requirements for Shh relate to the robust acquisition of appropriate cell type identities: In the mutant mice, follicular outer root sheath takes on an epidermal character, and certain HF disappear altogether, having adopted a strikingly mammary gland-like fate. Our study uncovers a multifaceted function for Shh in sculpting and maintaining the integrity and identity of the developing HF.

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