http://link.springer.com/chapter/10.1007/978-94-007-7687-6_7
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Abstract
Proper migration of
neurons is one of the most important aspects of early brain development.
After neuronal progenitors are born in their respective germinal
niches, they must migrate to their final locations to form precise
neural circuits. A majority of migrating neurons move by associating and
disassociating with glial fibers, which serve as scaffolding for the
developing brain. Cerebellar granule neurons provide a model system for
examination of the mechanisms of neuronal migration in dissociated and
slice culture systems; the ability to purify these cells allows
migration assays to be paired with genetic, molecular, and biochemical
findings. CGNs migrate in a highly polarized fashion along radial glial
fibers, using a two-stroke nucleokinesis cycle. The PAR polarity complex
of PARD3, PARD6, and an atypical protein kinase C (aPKC) regulate
several aspects of neuronal migration. The PAR polarity complex
regulates the coordinated movements of the centrosome and soma during
nucleokinesis, and also the stability of the microtubule cytoskeleton
during migration. PAR proteins coordinate actomyosin dynamics in the
leading process of migrating neurons, which are required for migration.
The PAR complex also controls the cell-cell adhesions made by migrating
neurons along glial cells, and through this mechanism regulates germinal
zone exit during prenatal brain development. These findings suggest
that the PAR complex coordinates the movement of multiple cellular
elements as neurons migrate and that further examination of PAR complex
effectors will not only provide novel insights to address fundamental
challenges to the field but also expand our understanding of how the PAR
complex functions at the molecular level.
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