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Abstract
In the past three decades, mounting evidence has revealed that specification of the
basic cortical neuronal classes starts at the time of their final mitotic divisions
in the embryonic proliferative zones. This early cell determination continues during
the migration of the newborn neurons across the widening cerebral wall, and it is
in the cortical plate that they attain their final positions and establish species-specific
cytoarchitectonic areas. Here, the development and evolutionary expansion of the neocortex
is viewed in the context of the radial unit and protomap hypotheses. A broad spectrum
of findings gave insight into the pathogenesis of cortical malformations and the biological
bases for the evolution of the modern human neocortex. We examine the history and
evidence behind the concept of early specification of neurons and provide the latest
compendium of genes and signaling molecules involved in neuronal fate determination
and specification.