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Journal of Neuroscience, Vol 6, 2676-2683, Copyright © 1986 by Society for Neuroscience
Weaver mouse cerebellar granule neurons fail to migrate on wild-type astroglial processes in vitro
ME Hatten, RK Liem and CA Mason
To study the regulation of glial-guided neuronal migration, we have
analyzed the behavior of cerebellar granule neurons purified from the
homozygous weaver (wv/wv) B6CBA-w mouse, an autosomal recessive genetic
mutation that suffers a failure of granule cell migration along Bergmann
glial processes (Rakic and Sidman, 1973a, b; Rezai and Yoon, 1972), on the
processes of astroglia purified from homozygous normal B6CBA-Aw-J-wv (+/+)
mouse cerebella. When co-cultured with normal astroglia, weaver granule
neurons failed to form neuron-glia contacts characteristic of migrating
neurons and impaired normal astroglial morphological differentiation.
Normal astroglial cells co-cultured with weaver granule cells had enlarged
cell somata with stunted processes and enlarged endfeet compared to normal
astroglia co-cultured with normal granule cells. In contrast, normal
neurons associated with weaver astroglia, forming tight appositions seen
for migrating neurons in vivo, and enhanced weaver astroglial morphological
differentiation. Weaver astroglia co-cultured with normal granule cells
contained a more normal complement of glial filaments and had a smaller
perikaryon with longer, more tapered processes than their counterparts
co-cultured with weaver neurons. These results suggest, in agreement with
the study of Goldowitz and Mullen (1982) on heterozygous mutant chimeras,
that the granule neuron is a primary site of action of the weaver gene, and
further support our previous findings that neuron-glia interactions
regulate astroglial morphological differentiation (Hatten, 1985).
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