The formation of periodic patterns is fundamental in biology. Theoretical models describing these phenomena have been proposed for feather patterning; however, no molecular candidates have been identified. Here we show that the feather tract is initiated by a continuous stripe of Shh, Fgf- 4, and Ptc expression in the epithelium, which then segregates into discrete feather primordia that are more strongly Shh and Fgf-4 positive. The primordia also become Bmp-2 and Bmp-4 positive. Bead-mediated delivery of BMPs inhibits local feather formation in contrast with the activators, SHH and FGF4, which induce feather formation. Both FGF-4 and SHH induce local expression of Bmp-4, while BMP-4 suppresses local expression of both. FGF-4 also induces Shh. Based on these findings, we propose a model that involves (1) homogeneously distributed global activators that define the field, (2) a position-dependent activator of competence that propagates across the field, and (3) local activators and inhibitors triggered in sites of individual primordia that act in a reaction-diffusion mechanism. A computer simulation model for feather pattern formation is also presented.
Bibliographical noteFunding Information:
We thank the following parties for providing reagents essential for this work: Genetics Institute, BMP-2, BMP-4, and FGF-4 pro- tein; Dr. A. P. McMahon, SHH protein and antibodies to SHH; Dr. C. Tabin, Shh, Ptc; Dr. Randy Johnson, Bmp-2, Bmp-4 probes; and Dr. G. Martin, Fgf-4 probes. We thank Dr. H. Hirase for help in computer programming. This work is supported by grants from NIH (C.M.C., R.B.W.), NSF (C.M.C.), and CTR (C.M.C.).
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Developmental Biology
- Cell Biology