The TGF-beta2 isoform is both a required and sufficient inducer of murine hair follicle morphogenesis.
Hair follicle development serves as an excellent model to study control of organ morphogenesis. Three specific isoforms of TGF-beta exist which exhibit a distinct pattern of expression during hair follicle morphogenesis. To clarify the still elusive role of these factors in hair follicle development, we have used a combined genetic and functional approach: analysis of hair follicle development in mice with disruptions of the TGF-beta1, 2, and 3 genes was coupled with a direct functional test of the effect of added purified factors on fetal hair follicle development in skin organ cultures. TGF-beta2 null mice exhibited a profound delay of hair follicle morphogenesis, with a 50% reduced number of hair follicles. In contrast to hair follicle development, growth and differentiation of interfollicular keratinocytes proceeded unimpaired. Unlike TGF-beta2-/- mice, mice with a disruption of the TGF-beta1 gene showed slightly advanced hair follicle formation, while lack of the TGF-beta3 gene did not have any effects. Treatment of wild-type, embryonic skin explants (E14.5 or E15.5) with TGF-beta2 protein in either soluble form or slow release beads induced hair follicle development and epidermal hyperplasia, while similar TGF-beta1 treatment exerted suppressive effects. Thus, the TGF-beta2 isoform plays a specific role, not shared by the other TGF-beta isoforms, as an inducer of hair follicle morphogenesis and is both required and sufficient to promote this process.
Foitzik
K
K
Cutaneous Biology Research Center, Massachussetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, 02129, USA.
Paus
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R
Doetschman
T
T
Dotto
G P
GP
D000818:Animals; D004627:Embryonic Induction; D004817:Epidermis / Q000196:embryology; D018859:Hair Follicle / Q000196:embryology*; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis; D009924:Organ Culture Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D016212:Transforming Growth Factor beta