Pleiotropic functions of neurotrophins in development

Neurotrophins are soluble growth factors known mainly for their roles in regulating the development of the mammalian nervous system. Two types of receptors mediate the actions of these polypeptides: the Trk family of tyrosine kinase receptors and the so-called p75 low-affinity NGF receptor. Neurotrophins and their receptors are highly expressed in the nervous system. Gene targeting approaches in the mouse have uncovered some of their functions in promoting survival and developmental maturation of certain types of neurons of the peripheral and central nervous system, confirming their critical role in neural development. Furthermore, the phenotypes observed in these mutants have demonstrated the specificity of the interactions between neurotrophins and their receptors. These families of genes are also widely expressed in a variety of non-neuronal systems throughout development, including the cardiovascular, endocrine, reproductive and immune systems. Our knowledge of neurotrophin functions in non-neuronal tissues is still fragmented and mostly indirect. Nevertheless, there is increasing evidence that neurotrophins may have broader physiological effects besides regulating neuronal survival and differentiation. Analysis of mice lacking neurotrophins or neurotrophin receptors promises to provide avenues for elucidating these functions.