Molecular mechanisms for generation of neural diversity and specificity: roles of polypeptide factors in development of postmitotic neurons.

Development of postmitotic neurons is influenced by two groups of polypeptide factors. Neurotrophic factors promote neuronal survival both in vivo and in vitro. Neuronal differentiation factors influence transmitter phenotypes without affecting neuronal survival. The list of neurotrophic factors is increasing partly because certain growth factors and cytokines have been shown to possess neurotrophic activities and also because new neurotrophic factors including new members of the nerve growth factor (NGF) family have been identified at the molecular level. In vitro assays using recombinant neurotrophic factors and distributions of their mRNAs and proteins have indicated that members of a neurotrophic gene family may play sequential and complementary roles during development and in the adult nervous system. Most of the receptors for neurotrophic factors contain tyrosine kinase domains, suggesting the importance of tyrosine phosphorylation and subsequent signal transduction for their effects. Molecules such as LIF (leukemia inhibitory factor) and CNTF (ciliary neurotrophic factor) have been identified as neuronal differentiation factors in vitro. At the moment, however, it remains to be determined whether or not the receptors for a group of neuronal differentiation factors constitute a gene family or contain domains of kinase or phosphatase activity. Synergetic combinations of neurotrophic and neuronal differentiation factors as well as their receptors may contribute to the generation of neural specificity and diversity.