ESSENTIAL ROLE OF ALPHA-6 INTEGRINS IN CORTICAL AND RETINAL LAMINATION

Extracellular matrix (ECM) is believed to play important roles in many aspects of nervous system development [1]. The laminins are ECM glyco proteins expressed in neural tissues and are potent stimulators of neu rite outgrowth in vitro [1-3]. Genetic approaches using Drosophila and Caenorhabditis elegans have demonstrated a role for laminin and a lam inin receptor in vivo in axon pathfinding and fasciculation, respectiv ely [4,5]. In higher organisms, however, the role of laminins in the d evelopment of the nervous system is poorly understood. Integrins alpha 6 beta 1 and alpha 6 beta 4 are major laminin receptors, A role for t he as integrin in neurulation has been reported in amphibians [6]. We previously described mice lacking integrin as; these mice died at birt h with severe skin blistering [7], Detailed analyses of integrin alpha 6(-/-) mice reported here revealed abnormalities in the laminar organ ization of the developing cerebral cortex and retina. Ectopic neurobla stic outgrowths were found on the brain surface and in the vitreous bo dy in the eye. Alterations of laminin deposition were found in mutant brains. Thus, this study provides evidence for an essential role of in tegrin-laminin interactions in the proper development of the nervous s ystem. These observations are particularly significant given the recen t report that human patients suffering from epidermolysis bullosa can carry mutations in ITGA6, the gene encoding the alpha 6 integrin chain [8,9].