FGF signals specifically regulate the structure of hair shaft medulla via IGF-binding protein 5

Abstract

Reciprocal interactions between the dermal papilla and the hair matrix control proliferation and differentiation in the mature hair follicle. Analysis of expression suggests an important role for FGF7 and FGF10, as well as their cognate receptor FGFR2-IIIb, in these processes. Transgenic mice that express a soluble dominant-negative version of this receptor in differentiating hair keratinocytes were generated to interfere with endogenous FGF signalling. Transgenic mice develop abnormally thin but otherwise normal hairs, characterised by single columns of medulla cells in all hair types. All structural defects and the accompanying changes of global gene expression patterns are restricted to the hair medulla. Forced transgenic expression of IGF-binding protein 5, whose expression level is elevated upon suppression of FGFR2-IIIb-mediated signalling largely phenocopies the defect of dnFgfr2-IIIb-expressing hairs. Thus, the results identify Igfbp5-mediated FGFR2-IIIb signals as a key regulator of the genetic program that controls the structure of the hair shaft medulla.

The Fibrotic Phenotype Induced by IGFBP-5 Is Regulated by MAPK Activation and Egr-1-Dependent and -Independent Mechanisms

“…Thus, MAPK activation by IGFBP-5 can now be added to the list of IGF-I-independent IGFBP-5 effects, which include stimulation of growth and IGF-I secretion by human intestinal smooth muscle cells, 22 migration of porcine vascular smooth muscle cells, 21 proliferation and activation of osteoblasts 28 -29 and osteoclasts, 30 and more recently induction of cellular senescence 31 and formation of hair shaft medulla. 32 IGFBP-5 contains a nuclear localization sequence, which targets the protein to the nuclear compartment. IGFBP-5 nuclear localization has been reported in human breast carcinoma cell lines, 27 Chinese hamster ovary cells, 33 and porcine vascular smooth muscle cells.…”

Sequencing and automated whole-genome optical mapping of the genome of a domestic goat (Capra hircus)

“…Other upregulated genes in secondary hair follicles include fibroblast growth factor 21 (GOAT_ENSP00000222157), which can promote the transition to catagen 37 , and casein kinase Iε(goat_ GLEAN_10015556), an important regulator of β-catenin in the Wnt pathway, which is one of the most important pathways in hair follicle development 38 .…”

(Neuro-)endocrinology of epithelial hair follicle stem cells

“…A c c e p t e d M a n u s c r i p t Botchkarev et al, 1999Peters et al, 1999Souza et al, 2006 Alonso and Fuchs, 2006 Aminik et al, 2007Paus and Foitzik, 2004Schlake, 2005aSchlake, 2005bStenn and Paus, 2001 Weger and Schlake,…”