0000000000241335
AUTHOR
Ralf Paus
Migration of Melanoblasts into the Developing Murine Hair Follicle Is Accompanied by Transient c-Kit Expression
Disruption of the c-Kit/stem cell factor (SCF) signaling pathway interferes with the survival, migration, and differentiation of melanocytes during generation of the hair follicle pigmentary unit. We examined c-Kit, SCF, and S100 (a marker for precursor melanocytic cells) expression, as well as melanoblast/melanocyte ultrastructure, in perinatal C57BL/6 mouse skin. Before the onset of hair bulb melanogenesis (i.e., stages 0–4 of hair follicle morphogenesis), strong c-Kit immunoreactivity (IR) was seen in selected non-mela-nogenic cells in the developing hair placode and hair plug. Many of these cells were S100-IR and were ultrastructurally identified as melanoblasts with migratory appearanc…
Control of murine hair follicle regression (catagen) by TGF‐β1in vivo
The regression phase of the hair cycle (catagen) is an apoptosis-driven process accompanied by terminal differentiation, proteolysis, and matrix remodeling. As an inhibitor of keratinocyte proliferation and inductor of keratinocyte apoptosis, transforming growth factor beta1 (TGF-beta1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF-beta1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF-beta1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF-beta1 null mice and age-matched wild-type …
Kit Is Expressed by Epithelial Cells In Vivo
In mammalian skin, stem cell factor (SCF) regulates the proliferation and maturation of mast cells and melanocytes, which are thought to be the only cutaneous cells that express the Kit-tyrosine kinase receptor (Kit) and respond to epithelial and mesenchymal-derived SCF. We previously had noted, however, the presence of Kit+ cells in murine hair follicles, in an introepithelial tissue compartment devoid of melanocytes and mast cells. Here we have identified the nature of this Kit+ population of cells in hair follicles of C57BL/6 mice. Anagen hair follicles showed strong Kit immunoreactivity not only in the pigmentary unit above the follicular dermal papilla but also in a much more proximall…
Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness
Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (P<5 × 10−8, METAL) of which 23 have not been reported previously. The 63 loci explain ∼39% of the phenotypic variance in MPB and highlight several plausible candidate genes (FGF5, IRF4, DKK2) and pathways (melatonin signalling, adipogenesis) that are likely to be implicated in the key-pathophysiological features of MPB and may represent promising targets for the de…