Making map of the mind: molecular mechanisms of neuronal migration
The identity, synaptic relationship and, ultimately, function of neurons is defi ned by their position. It is particularly evident in the cerebral cortex where neurons acquire their position by active migration before birth from multiple sites of origin and involve complex molecular events and cell–cell interactions. We have used a variety of in vitro and in vivo assays show how specifi c genes, encoding signaling and morphoregulatory molecules and their receptors cooperate in orchestrating various components of migration such as the mode of neuronal proliferation, phenotype determination, establishment of polarity, detachment from the local substrate and rate of migration to the proper position in the cortex. Interestingly, some of these genes and molecules are also implicated in the pathogenesis of cognitive disorders such as schizophrenia, mild mental retardation, childhood epilepsy and autism. In addition, we found that the rate of neuronal migration and precise inside-to-outside sequence of their deployment can be disrupted by exposure of embryo to various physical, chemical, and biological agents. Disruption or even slowing down of neuronal migration by either genetic or environmental factors results in gross heterotopias or in subtle abnormalities of neuronal positions that eventually affect the pattern of synaptic circuits and ultimately may cause variety of idiopathic disorders of highest cognitive function.