Molecular evidence for an activator–inhibitor mechanism in development of embryonic feather branching

doi:10.1073/pnas.0500781102

Molecular evidence for an activator–inhibitor mechanism in development of embryonic feather branching

^*Department of Anatomy, 1300 Bardeen, University of Wisconsin, Madison, WI 53706; ^§Department of Biological Statistics and Computational Biology, 101 Biotech, Cornell University, Ithaca, NY 14853; ^¶Max Plank Institute für Entwicklungsbiologie, Abt. Evolutionsbiologie, Spemanstrasse 35, 72072 Tübingen, Germany; and ^∥Department of Ecology and Evolutionary Biology, and Peabody Museum of Natural History, Yale University, P. O. Box 208105, New Haven, CT 06520

Edited by Kathryn V. Anderson, Sloan–Kettering Institute, New York, NY, and approved June 24, 2005 (received for review January 29, 2005)

Abstract

The developmental basis of morphological complexity remains a central question in developmental and evolutionary biology. Feathers provide a unique system to analyze the development of complex morphological novelties. Here, we describe the interactions between Sonic hedgehog (Shh) and bone morphogenetic protein 2 (Bmp2) signaling during feather barb ridge morphogenesis. We demonstrate that activator–inhibitor models of Shh and Bmp2 signaling in the tubular feather epithelium are sufficient to explain the initial formation of a meristic pattern of barb ridges and the observed variation in barb morphogenesis in chick natal down feathers. Empirical tests support the assumptions of the model that, within the feather ectoderm, Shh (activator) up-regulates its own transcription and that of Bmp2 (inhibitor), whereas Bmp2 signaling down-regulates Shh expression. More complex models incorporating a second activator and dorsal/ventral polarized modification of activator signaling can produce all of the barb morphogenesis patterns observed during the growth of more complex branched pennaceous feathers: new barb ridge formation, helical growth, and barb ridge fusion. An integrated model of feather morphogenesis and evolution suggests that plumulaceous feather structure evolved by the establishment of activator–inhibitor interactions between Shh and Bmp2 signaling in the basal epithelium of the feather germ. Subsequently, pennaceous feather structure evolved through the integration of barb ridge morphogenesis with a second, local inhibitor and a dorsal/ventral signal gradient within the feather. The model is congruent with paleontological evidence that plumulaceous feathers are primitive to pennaceous feathers.

Footnotes

↵ ‡ To whom correspondence may be addressed. E-mail: matthew.harris{at}tuebingen.mpg.de or richard.prum{at}yale.edu.
↵ † Present address: Max Plank Institute für Entwicklungsbiologie, Abt. Genetik, Spemanstrasse 35, 72072 Tübingen, Germany.
Author contributions: M.P.H. and R.O.P. designed research; M.P.H., S.W., and H.M. performed research; J.F.F. contributed new reagents/analytic tools; R.O.P. analyzed data; and M.P.H. and R.O.P. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: Bmp2, bone morphogenetic protein 2; D/V, dorsal/ventral; Shh, Sonic hedgehog; BCIP, 5-bromo-4-chloro-3-indolyl phosphate.