Transforming growth factor-β receptor type I and type II expression during murine hair follicle development and cycling

Although the TGF-β family of growth factors probably regulates skin and hair follicle development, its exact role is still quite ill-defined. Here, we characterize the correlative expression pattern of the interdependent high affinity receptor proteins for TGF-β1 and TGF-β3, TGF-β receptor type I (TGF-βRI) and TGF-β receptor type II (TGF-βRII), during hair follicle development and cycling in C57BL/6 mice. During neonatal follicle development, TGF-βRII immunoreactivity is confined to epithelial cells. Focal epidermal TGF-βRII expression is seen even before actual hair placode formation. In contrast to the TGF-βRII immunoreactivity in the outer root sheath, precortical hair matrix and inner root sheath cells were TGF-βRII negative during hair bulb morphogenesis. TGF-βRI (Alk-5) immunoreactivity largely overlapped the TGF-βRII expression pattern, but was more widespread. During hair follicle cycling in adolescent mice, TGF-βRII immunoreactivity was restricted to follicles, and was strikingly hair cycle dependent (maximal immunoreactivity; anagen VI and early catagen). Again, TGF-βRI (Alk-5) immunoreactivity co-localized with TGF-βRII immunoreactivity, but was more extensive. Reverse transcriptase polymerase chain reaction analysis of TGF- βRII mRNA confirmed peak transcript levels in back skin with most hair follicles in the anagen VI transformation. mRNA levels of TGF-βRI (Alk-5) did not vary significantly during the hair cycle, whereas those of TGF-βRI (threonine-serine kinase 7 L) declined during early anagen, and were maximal during the anagen-catagen transition. This provides a basis for defining the choreography of TGF-β-related signalling during hair follicle morphogenesis and cycling, introduces intraepidermal TGF-βRII immunoreactivity as a marker for imminent follicle development, and supports the concept that both TGF- βRII and TGF-βRI stimulation is involved in, but not restricted to, the control of catagen induction.