Epigenetic rules for expression of cell adhesion molecules during morphogenesis

From very early developmental times, cell adhesion molecules (CAMs) play key roles in linking cells together and regulating cell movement. By virtue of their capacity to link epithelia and condense mesenchyme, CAMs can act as mechanochemical regulators of morphogenesis. In the vertebrate species examined so far, CAMs appear in ordered sequences on cell surfaces during development. In this paper, evidence is reviewed indicating that the sequential expression of CAMs on cell surfaces at a variety of sites of embryonic induction follows a set of modulation rules that are first discernible at early gastrulation. These rules are related to the adhesion of cells in collectives and to the establishment of borders between such collectives. After gastrulation, all mesenchymal conversions employ N-CAM and show changes in its prevalence in a transition N----0----N where 0 means low or undetectable amounts of the CAM (rule I). In contrast, epithelia modulate from a state in which N-CAM and L-CAM appear simultaneously to the expression of only one or the other of these primary CAMs (rule II). At a variety of induction sites, cell collectives obeying rule I are found in proximity to cell collectives obeying rule II. During the morphogenesis of complex structures such as the feather or the optic placode, one can see a recursive application of these rules, reflecting the formation of significant histological boundaries within which the expression of gene products other than CAMs can lead to great morphological diversity. It is suggested that the genes for CAMs are regulated independently from and prior to those specifying intracellular proteins in a given tissue. According to this proposal, the existence of the epigenetic rules governing CAM expression reflects the evolutionary conservation of a key means of establishing tissue and animal form through the mechanochemical regulation of processes such as cell division, movement and death.