Glycosylphosphatidylinositol Anchored Recognition Molecules That Mediate Intercellular Adhesion and Promote Neurite Outgrowth

Abstract

Neuronal development can be divided into several well defined phases which include expansion of progenitor cells, cessation of mitosis, expression of genes that define the initial neuronal phenotype and, finally, elaboration of complex axonal and dendritic arbors. Much of this, and in particular the latter phase, is not pre-determined within the genome of individual cells, but is controlled by interactions of the cell with its microenvironment. A variety of strategies have been adopted to elucidate the molecular basis of the recognition events that underly development of the nervous system. Immunological techniques, often coupled with in vitro assays that measure perturbation of cell-cell interactions (for example inhibition of specific cell-cell adhesion or defasciculation of neurite bundles), have resulted in the identification of a large number of neuronal cell surface glycoproteins that may play key roles in the above. Two important concepts have recently emerged: firstly, most of the neuronal glycoproteins identified to date can be accommodated within one of three gene families, namely the integrin family of receptors that primarily interact with extracellular matrix components (Reichardt and Tomaselli, 1991), the family of calcium dependent cell adhesion molecules called Cadherins (Takeichi, 1991) or the immunoglobulin gene family (Williams, 1987). The number of molecules in each family continues to increase and it is highly likely that many aspects of neural development, and in particular axonal growth and guidance, will involve the orchestration of function of several members of each family. The second important concept to emerge is that a large number of these glycoproteins are attached to the cell membrane via covalent linkage to membrane lipids and in particular glycosylphosphatidylinositol (GPI).