Role of the basement membrane in neurogenesis and repair of injury in the central nervous system.

Abstract

Although remarkable progress has been made during the last two decades concerning the biosynthesis, expression and assembly of extracellular matrix (ECM) macromolecules in nonneural cells, we are still far from a complete understanding of the role and function of the ECM and the basement membrane (BM) in the central nervous system (CNS). With the aid of correlative light and electron microscopic, Golgi and immunohistochemical studies of the developing neural tube of both early human fetus and mouse, we have shown that the establishment of the pial-glial barrier (PGB) is one of the earliest histogenetic events in neurogenesis. This is accomplished by coordinated interaction among the processes of radial glia, various ECM components, and mesenchymal cells at the pial surface, with the formation of a BM that tightly abuts the glia limitans. The PGB and the BM appear to be critical to the migration and final positioning of neurons and to the differentiation of the laminar cortical pattern within the developing neopallium. This hypothesis is further supported by our study of the brain of a human newborn infant in whom multiple sites of disruption of the BM and PGB resulted in abnormal neuronal migration and massive ectopia of neurons within the subarachnoid space, with abnormal cortical lamination. Finally, studies of the experimental cryogenic injury to the neonatal rat cerebrum have shown that the final positioning of neurons within the developing cortical plate appears to depend largely on the reconstitution of the BM and PGB, which presumably provide crucial positional signals for migrating neurons. Also, one of the essential reparative features seen following cryogenic injury to the adult rat cerebrum is an orderly and dynamic interaction between various ECM components and neural cells, resulting in the formation of the BM.