A TIME-COURSE STUDY OF THE ALTERATIONS IN THE DEVELOPMENT OF THE HAMSTER CEREBELLAR CORTEX AFTER DESTRUCTION OF THE OVERLYING MENINGEAL CELLS WITH 6-HYDROXYDOPAMINE ON THE DAY OF BIRTH

This study is a chronological analysis of 6-hydroxydopamine-induced al terations in development of the hamster cerebellar cortex. This treatm ent destroys the overlying meningeal cells, the sequelae of which incl ude (i) a thinning of the external granular layer over the folial apic es and a thickening in the region of the prospective fissures, reflect ing a retardation of the growth of the cerebellar cortex, accompanied by displacement of the normally superficialmost GFAP-positive external granular layer cells into deeper parts of the external granular layer ; (ii) a retardation of multiplication of Golgi epithelial cells which colonize the rostral third of the Purkinje cell layer so that their n umbers decrease in the rostralmost folia; (iii) disturbed morphologica l and biochemical differentiation of the Golgi epithelial cells and th eir processes, the growing radial Bergmann glial fibres which detach f rom the pial surface and branch within the external granular layer, ca using a failure in endfeet formation at the superficial glia limitans, loss of characteristic radial morphology, with the adoption of a mult ipolar form, and normal or increased GFAP expression and decreased S-1 00 expression; (iv) fragmentation of the external granular layer beyon d P5 to P7 with loss of the regular lamination and foliation of the ce rebellar cortex, characterized by a completely random distribution of fragments of Purkinje cell layer, molecular zone and internal granular layer. We conclude that the destruction of meningeal cells interferes with the establishment and stabilization of both the external granula r layer and the secondary radial glial scaffold composed of Golgi epit helial cells, whose proliferation, growth and differentiation is subse quently disturbed. The failure to stabilize the external granular laye r and to form a normal secondary radial glial scaffold is, in turn, re sponsible for the disruption of the regular laminar deposition of the neurons of the cerebellar cortex.