The developing CNS: a scenario for the action of proinsulin, insulin and insulin-like growth factors

The multifunctional cytokines of the family of insulin and insulin-like growth factors (IGFs) have not yet gained general recognition as essential cell signals for the development of the vertebrate nervous system. This is, in part, a consequence of previous constraints in our thinking, focused for many years on the endocrine roles of these factors in late mammalian development and postnatal stages. The cellular distribution of the components of the insulin and IGFs signalling system in the developing mammalian and avian CNS is remarkably conserved. While receptors are widespread, the much less abundant factors and modulatory proteins are highly regulated in time and space. Progression of neural development through the steps of cell proliferation, differentiation, maturation and survival is stimulated, at least in culture, by proinsulin and insulin and the IGFs. Thus, these factors might be important autocrine and paracrine signals during development of the CNS.