Further Development 14.3: The Scaffolding of Bergmann Glia in the Cerebellum

Brain Growth

One mechanism thought to be important for positioning young neurons in the developing mammalian brain is glial guidance (Rakic 1972; Hatten 1990). Throughout the cortex, neurons are seen to ride a “glial monorail” to their respective destinations. In the cerebellum, the granule cell precursors travel on the long processes of the Bergmann glia, a type of radial glial cell that extends one to two thin processes throughout the germinative neuroepithelium (see Figure 14.4B; Rakic and Sidman 1973; Rakic 1975). As Figure 1 illustrates, this neuron-glia interaction is a complex and fascinating series of events involving reciprocal recognition between glia and newly postmitoic neurons (Hatten 1990; Komuro and Rakic 1992).

It appears that the migration of newborn neurons involves the loss of those adhesion molecules that linked the neuron to the germinal layer cells and the acquisition of a set of adhesion molecules that attach it to the glia (Famulski et al. 2010). The molecules involved in this adhesion were discovered through a number of mouse mutants that could not keep their balance and were given names such as reeler, staggerer, and weaver that reflected their movement problems (Falconer 1951). In reeler brains, glial cells lack the extracellular matrix protein Reelin that permits the neurons to bind to them. Another adhesion protein, astrotactin, is needed by granule cell neurons to maintain their adhesion to the glial process. If the astrotactin on a neuron is masked by antibodies to that protein, the neuron will fail to adhere to the glial processes (Edmondson et al. 1988; Fishell and Hatten 1991). The direction of this migration appears to be regulated by a complex series of events orchestrated by brain-derived neurotrophic factor (BDNF), a paracrine factor made by the internal granular layer (Zhou et al. 2007).

Figure 1 Neuron-glia interactions in the mouse. (A) Diagram of a cortical neuron migrating on a glial cell process. (B) Sequential photographs of a neuron migrating on a cerebellar glial process. The leading process has several filopodial extensions. The neuron can reach speeds of about 40 mm per hour as it travels.

Literature Cited

Edmondson, J. C., R. K. H. Liem, J. E. Kuster and M. E. Hatten. 1988. Astrotactin: A novel neuronal cell surface antigen that mediates neuronal-astroglial interactions in cerebellar microcultures. J. Cell Biol. 106: 505–517.

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Famulski, J. K. and 6 others. 2010. Siah regulation of Pard3A controls neuronal cell adhesion during germinal zone exit. Science 330:1834–1838.

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Fishell, G. and M. E. Hatten. 1991. Astrotactin provides a receptor system for CNS neuronal migration. Development 113: 755–765.

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Hatten, M. E. 1990. Riding the glial monorail: A common mechanism for glial-guided neuronal migration in different regions of the mammalian brain. Trends Neurosci. 13: 179–184.

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Komuro, H. and P. Rakic. 1992. Selective role of N-type calcium channels in neuronal migration. Science 257: 806–809.

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Rakic, P. 1972. Mode of cell migration to superficial layers of fetal monkey neocortex. J. Comp. Neurol. 145: 61–83.

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Rakic, P. 1975. Cell migration and neuronal ectopias in the brain. In D. Bergsma (ed.), Morphogenesis and Malformations of Face and Brain. Birth Defects Original Article Series, vol. 11, no. 7. Alan R. Liss, New York, pp. 95–129.

Rakic, P. and R. L. Sidman. 1973. Organization of cerebellar cortex secondary to deficit of granule cells in weaver mutant mice. J. Comp. Neurol. 152: 133–162.

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Zhou, P. and 9 others. 2007. Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors. Neuron 55: 53–68.

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