The role of long range, local and direct signalling molecules during chickfeather bud development involving the BMPs, Follistatin and the Eph receptor tyrosine kinase Eph-A4

The development of the feather buds during avian embryogenesis is a classic example of a spacing pattern. The regular arrangement of feather buds is a chieved by a process of lateral inhibition whereby one developing feather b ud prevents the formation of similar buds in the immediate vicinity. Latera l inhibition during feather formation implicates a role of long range signa lling during this process. Recent work has shown that BMPs are able to enfo rce lateral inhibition during feather bud formation. However these results do not explain how the feather bud escapes the inhibition itself. We show t hat this could be achieved by the expression of the BMP antagonist, Follist atin. Furthermore we show that local application of Follistatin leads to th e development of ectopic feather buds. We suggest that Follistatin locally antagonises the action of the BMPs and so permits the cellular changes asso ciated with feather placode formation. We also provide evidence for the rol e of short range signalling during feather formation. We have correlated ch anges in cellular morphology in feather placodes with the expression of the gene Eph-A4 which encodes a receptor tyrosine kinase that requires direct cell-cell contact for activation. We show that the expression of this gene precedes cellular reorganisation required for feather bud formation. (C) 19 99 Elsevier Science Ireland Ltd. All rights reserved.