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The roles of growth factors and neural activity in the development of the neocortex.

Previous research on primarily the peripheral nervous system has shown that soluble growth factors help control key developmental events by contributing to dynamic autocrine and paracrine signalling systems. Much less is known about the roles of these substances in neocortical development. Using cell and tissue culture paradigms, we have demonstrated that soluble growth factors are produced by the neocortex and its subcortical targets, and that these tissues can respond to them. There are several possible functions for these factors in neocortical development in vivo: they may initiate axonal growth from neocortical neurons and/or their afferents; accelerate or guide that growth; and/or play a role in the later refinement of connections. Although none of these possibilities can be excluded, the existing evidence strengthens the hypothesis that soluble growth factors are important for the early postnatal growth and refinement of neocortical connections, when their levels of release may be regulated by neocortical activity. At present we do not know which growth factors are involved in these processes, but the results of preliminary experiments indicate that neurotrophins and fibroblast growth factor are prime candidates.