What are the signals that regulate the establishment, development and differentiation of radial glial cells, a key substrate for neurogenesis and neuronal migration in cerebral cortex?
Among the early developing cells within the mammalian brain are highly polarized neural precursor cells, radial glia, which give rise to most cortical neurons and guide their appropriate migration and placement. The polarity of radial glial cells is manifested by the positioning of a pear shaped cell soma in the ventricular zone (VZ) and a long, slender process extending from the VZ towards pia. Polarized radial glial cells can divide symmetrically or asymmetrically. Symmetric radial glial divisions give rise to two daughter radial glial cells and occur primarily during the early stages of cortical development to expand the radial glial population. Asymmetric divisions of radial glia result in a daughter neuron and a radial glial cell or an intermediate precursor. The pially-directed radial process provides a permissive and instructive scaffolding for the oriented migration of newly generated neurons. As neurogenesis and neuronal migration ends, radial glia transform to give rise to glial progeny. Disruptions in polarized radial glial scaffold could therefore affect both neurogenesis and migration, leading to aberrant generation, positioning and connectivity of neurons in cerebral cortex. However, little is known about how the polarized radial glial scaffold is constructed and maintained during corticogenesis. We therefore aim to identify the molecular regulators and mechanisms involved in this process.
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