The role of the Reelin pathway in cortical development

摘要

In the mammalian central nervous system, the majority of neuronal cells derive from a small population of stem cells that proliferate in the ventricular zone. Initially, progenitor cells divide equally, giving rise to more stem cells (expansion phase). Subsequently, cell division gives rise to daughter kcells that exit the cell cycle and become postmitotic (neurogenesis). In the cerebral cortex, committed neuroblasts migrate along radial fibres towards the surface of the brain (migration phase). At the end of their migration, differentiating neurons detach from the radial fibres and acquire their specific phenotype. Birthdating studies demonstrated that cohorts of neurons born at approximately the same time end up at the same level in the radial dimension of the cortex and acquire similar morphologies and chemical phenotypes, giving rise to the characteristic six layers of the mammalian neocortex. The formation of these layers follows an 'inside-out' gradient as younger neurons bypass older cells (Caviness, 1982). Therefore, at the end of neurogenesis, early neuronal populations are found deep in the cortex whereas neurons born towards the end of cortico genesis occupy more superficial layers. The formation of cortical layers depends on the activity of several genes. Some of these genes have been recently discovered because their disruption in naturally occurring or induced mutant mice results in aberrant brain development.