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).
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