Cell adhesion and morphogenesis: the regulator hypothesis.

A sequence for the genetic and molecular regulation of morphogenesis is proposed in terms of the regulator hypothesis which is intended to provide a specific molecular framework relating developmental genetics to evolution. The hypothesis derives from an analysis of the interactive morphogenetic roles of the primary processes of cell adhesion, cell movement, and embryonic induction during regulative development. According to the regulator hypothesis, the genes for cell adhesion molecules (CAMs) are expressed in schedules that are prior to and largely independent of those for cytodifferentiation. The expressed CAMs act as regulators of the overall patterns of those morphogenetic movements that are essential for inductive sequences or early milieu-dependent differentiations. It is proposed that, during evolution, natural selection eliminates those organisms in which variants of CAM gene expression or of morphogenetic movements or of both result in interruptions in the inductive sequence. Under this assumption, more than one (but not all) combinations of these two variables will lead to stabilization of the order of inductive sequences and of the body plan in a variety of species. Moreover, small variations in the pattern of action of regulatory genes for CAMs in those organisms that are not selected against could lead to large changes in animal form within relatively short periods of evolutionary time. The experimental bases for the regulator hypothesis are reviewed here in terms of the molecular properties of CAMs and their known spatio-temporal sequences of expression during early embryogenesis.