The initiation and morphogenesis of cutaneous appendages depend on a series of reciprocal signaling events between the epithelium and mesenchyme of the embryonic skin. In the development of feather germs, early dermal signals induce the formation of epidermal placodes that in turn signal the mesoderm to form dermal condensations immediately beneath them. We find a spatially and temporally restricted pattern of transcription for the genes that encode fibroblast growth factor (FGF) 2 and FGF receptor (FGFR) 1 in developing feather germs of the chicken embryo. FGF-2 expression is restricted to the epidermal placodes, whereas FGFR-1 expression is limited to the dermal condensations. Transcription of these genes could not be detected in skins of scaleless (sc/sc) embryos that fail to develop feathers as a result ofan ectodermal defect. Treatment of sc/sc skins with FGF-2 results in the formation of feathers at the site of application of the growth factor and the induced feathers express FGFR-1 in their dermal condensations. Thus, we have established FGF-2 as an epidermal signal in early feather germ formation. The observation that FGF-2 can rescue the mutant phenotype of sc/sc embryos suggests that FGF-2 either is, or is downstream from, the signal that the sc/sc mutant ectoderm fails to generate.

In a previous report, we showed that fibroblast growth factor-2 (FGF-2) is a signal produced by epidermal placode cells during feather development and that this growth factor can induce feathers in scaleless mutant skins that fail to form feathers due to a defective epidermis (Song et al., [1996] Proc Natl Acad Sci USA 93:10246 -10249). Here, we test whether FGF-2 is sufficient to induce dermal condensations, structures that normally form under the control of signals from the epidermal placode and are identified on the basis of aggregation of cells, the expression of FGF receptor-1 and bone morphogenetic protein-2 transcripts and the cessation of proliferation of the condensed cells. By using denuded 8-day scaleless dermis as a test system, we have established that FGF-2 is sufficient to induce dermal condensation. We suggest that the primary effect of FGF-2 is an increase in cellular density mediated through cell migration, followed by the expression of dermal condensation-specific genes and cessation of cell proliferation. The FGF-2 effect can be abolished by heparin, suggesting the involvement of heparan sulfate proteoglycans (HSPGs) in growth factor signaling. The spatiotemporal expression of syndecan-3 during feather development suggests that this cell-surface HSPG may be involved in the response of competent embryonic skin dermis to FGF-2. Developmental Dynamics 231:741-749, 2004.