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

Abstract

This study is a chronological analysis of 6-hydroxydopamine-induced alterations in development of the hamster cerebellar cortex. This treatment destroys the overlying meningeal cells, the sequelae of which include (i) a thinning of the external granular layer over the folial apices and a thickening in the region of the prospective fissures, reflecting 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 numbers decrease in the rostralmost folia; (iii) disturbed morphological and biochemical differentiation of the Golgi epithelial cells and their processes, the growing radial Bergmann glial fibres which detach from the pial surface and branch within the external granular layer, causing a failure in endfeet formation at the superficial glia limitans, loss of characteristic radial morphology, with the adoption of a multipolar form, and normal or increased GFAP expression and decreased S-100 expression; (iv) fragmentation of the external granular layer beyond P5 to P7 with loss of the regular lamination and foliation of the cerebellar 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 granular layer and the secondary radial glial scaffold composed of Golgi epithelial cells, whose proliferation, growth and differentiation is subsequently disturbed. The failure to stabilize the external granular layer and to form a normal secondary radial glial scaffold is, in turn, responsible for the disruption of the regular laminar deposition of the neurons of the cerebellar cortex.

GPR56-Regulated Granule Cell Adhesion Is Essential for Rostral Cerebellar Development

“…The cerebellar phenotype in Gpr56 −/− mice is strikingly similar to those observed when the meninges overlying the cerebellum are ablated at birth using 6-hydroxydopamine (Sievers et al, 1985; von Knebel Doeberitz et al, 1986; Sievers et al, 1994b). This raises the intriguing possibility that the meninges are necessary for GPR56 function in rostral cerebellar development, potentially as a source of the GPR56 ligand.…”

Extracellular Matrix: Functions in the Nervous System

“…A number of studies have shown that the pial BL is crucial for neocortical development. Removal of the BL leads to detachment of RGC fibers, affecting RGC survival and cortical lamination von Knebel Doeberitz et al 1986;Sievers et al 1994;Radakovits et al 2009). Laminins are major components of the BL (Timpl et al 1979) and are also present in the VZ of the developing neocortex (Campos et al 2004;Lathia et al 2007).…”

Glial fibrillary acidic protein in the brain of the caecilian Typhlonectes natans (Amphibia, Gymnophiona): an immunocytochemical study

“…The loss of lamination observed in many caecilian species (Wake 1985) may be a consequence of the alteration of retinal glial structures. Indeed, intact radial glial structures are necessary for the formation of neuronal layers in the cerebellum (Rakic 1971;Hatten 1990;Sievers et al 1994). The initial changes observed in caecilian retinal Müller cells might involve those of the cytoskeleton, e.g.…”