Homeobox-Containing Genes and GAP Junctional Communication in Pattern Formation during Chick Limb Development

Abstract

Elucidating the mechanisms involved in eliciting the formation of the various skeletal elements of the limb in their appropriate position and sequence along the anterior-posterior (A-P) axis is fundamental to understanding normal and abnormal vertebrate limb development. The zone of polarizing activity (ZPA) at the posterior margin of the developing limb bud appears to be the source of a diffusible morphogen, possibly retinoic acid, that becomes distributed in a graded fashion across the A-P axis of the limb, and specifies the A-P positional values of the skeletal elements of the limb according to its local concentration (Brickell and Tickle, 1989; Eichele, 1989). Homeobox-containing genes have been implicated in the regulation of pattern formation during development, and several homeobox genes exhibit spatially-restricted and temporally-regulated patterns of expression during vertebrate limb development (Oliver et al., 1988, 1989; Dolle et al., 1989; Hill et al., 1989; Robert et al., 1989; Wedden et al., 1989). In the present manuscript we describe some of our current studies on the isolation and characterization of several homeobox genes expressed during embryonic chick limb development, and present evidence indicating that some of these genes are expressed in a graded fashion along the A-P axis of the chick limb bud as positional values along the A-P axis are being specified. We also report on studies indicating that intercellular signalling via gap junctions may be involved in specification of pattern along the A-P axis of the chick limb bud.