Cell fate and axonal projections from the cerebral cortex

The formation of axonal connections in the nervous system involves cell-specific decisions of the growth cone. In this article we examine the contribution of early fate decisions to axonal pathfinding. Evidence is accumulating that different neuronal cell types in the cerebral cortex are specified during their final mitosis. It would seem that cortical projection neurons are pre-specified to choose particular pathways, since the newly generated neurons send out their axons in the correct direction from the onset of outgrowth. Pathfinding decisions that are made much later during development, such as the recognition of specific target-derived chemoattractants and the retraction of inappropriate axon collaterals, also seem to be at least partially pre-specified at much earlier developmental stages. Hence, the early determination of a neuron's phenotype includes the specification of axonal growth occuring over a protracted phase of development. Understanding more about the regulative events targeted to the growth cone should help us to unravel the decisions made by this specialized neuronal organelle.