Neurotrophins and cerebellar development.

Neurotrophins are structurally related molecules which regulate the survival and differentiation of various populations of neurons during development. In the cerebellum, the neurotophins and their Trk receptors are expressed at a relatively high level, suggesting an important function for these factors during development. There is also a tight age-dependent and spatial regulation of the molecules in the various cerebellar neurons. Previous studies have shown that BDNF and NT-3 have distinct biological effects on survival and differentiation of cerebellar granule neurons and Purkinje cells. Aside from acting as survival and differentiation factors, the neurotrophins could also have more subtle effects on neuronal function. It is also becoming increasingly evident, not the least from studies in neurotrophin deficient and in cerebellar mutant mice, that the neurotrophins act in concert with other factors and molecules in controlling neuronal development. We will here review some of the recent developments in the neurotrophin field with regard to cerebellum and also discuss what is known about the signaling event following stimulation of cerebellar neurons with BDNF and NT-3. The characterization of specific maturation stages and of genes which are involved and regulated by neurotrophins in developing cerebellum will help us to understand the processes of neuronal survival and differentiation in general.