Electron microscopic analysis of postnatal histogenesis in the cerebellar cortex of staggerer mutant mice

Abstract

Postnatal development of the cerebellar cortex has been compared in staggerer mutant and unaffected littermate mice. From postnatal day 3 to about day 21 the external granular layer in staggerer mice is decreased in thickness and area, and the number of postmitotic granule cell neurons is reduced. Those granule cells that are generated seem to differentiate normally, with the remarkable exception that they form only primitive junctions with Purkinje cell dendritic shafts. These specialized junctions are not superseded by the normal parallel fiber:Purkinje spine synapses and disappear by the third week. Purkinje cell somata and dendrites are smaller than normal at all stages examined. The dendrites are not confined to the sagittal plane as in the normal and, unique among mutant or other animals described to date, they exhibit virtually no branchlet spines. All other cortical synaptic relations of granule and Purkinje cells, including climbing fiber:Purkinje spine synapses, appear qualitatively normal. However, by 28 days virtually all staggerer granule cells have degenerated. While the primary genetic defect remains unknown, we postulate that the morphological abnormalities may be attributable to a block in the normal developmental relationship between granule cells and Purkinje cells. The small cell size and failure to form branchlet spines suggest that the Purkinje cell abnormality may be closer to the primary effect of the mutant gene than the more flagrant hypoplasia and degeneration of granule cell neurons.

Rorα, a pivotal nuclear receptor for Purkinje neuron survival and differentiation: From development to ageing

“…By electronic microscopy, the presence of attachment plates between Purkinje cell dendrites and parallel fibers has been described (61), suggesting that parallel fibers form transient primitive junctions with the Purkinje cell dendritic shaft, but attachment plates then fail to develop into functional synapses (61). In contrast, qualitatively normal dendritic spines and synapses are formed with climbing fibers (31,(58)(59)(60). However, there is a failure in the developmental regression of the Purkinje cell polyinnervation by climbing fibers (62,63).…”

Cloning and Expression of a Rat Brain Interleukin-1β-Converting Enzyme (ICE)-Related Protease (IRP) and Its Possible Role in Apoptosis of Cultured Cerebellar Granule Neurons

“…During cerebellar development, for example, granule neurons, which are among the most abundant neuronal phenotype, are generated postnatally in the external germinal layer where they differentiate, migrate to the granule layer, and finally are innervated by mossy fiber axons (Altman, 1972). More than 50% of these neurons die before completion of their postnatal migration (Landis and Sidman, 1978). The precise nature of this fatal selection, however, remains a mystery.…”

Expression of the weaver gene in dopamine-containing neural systems is dose-dependent and affects both striatal and nonstriatal regions

“…This autosomal recessive mutation results in a lack of granule cells (Sidman et al, 1962), reduced numbers of Purkinje cells (Herrup and Mullen, 1979), and malformation of the residual Purkinje cells (Landis and Sidman, 1978;Sotelo. 1975).…”