BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties.
Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial-mesenchymal cross-talk necessary to make hair.
Rendl
Michael
M
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10021, USA.
Polak
Lisa
L
Fuchs
Elaine
E
D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D017403:In Situ Hybridization; D019426:Integrases / Q000378:metabolism; D008024:Ligands; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D010006:Osteoblasts; D010012:Osteogenesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D008024:Ligands; D011956:Receptors, Cell Surface; D052005:Bone Morphogenetic Protein Receptors, Type I; C045073:Cre recombinase; D019426:Integrases