ABNORMAL CEREBELLAR DEVELOPMENT AND FOLIATION IN BDNF- - MICE REVEALSA ROLE FOR NEUROTROPHINS IN CNS PATTERNING/

While target-derived neurotrophins are required for the survival of de veloping neurons in the PNS, the functions of neurotrophins in the CNS are unclear. Mice with a targeted gene deletion of brain-derived neur otrophic factor (BDNF) exhibit a wide-based gait. Consistent with this behavioral evidence of cerebellar dysfunction, there is increased dea th of granule cells, stunted growth of Purkinje cell dendrites, impair ed formation of horizontal layers, and defects in the rostral-caudal f oliation pattern. These abnormalities are accompanied by decreased Trk activation in granule and Purkinje cells of mutant animals, indicatin g that both cell types are direct targets for BDNF. These data suggest that BDNF acts as an anterograde or an autocrine-paracrine factor to regulate survival and morphologic differentiation of developing CNS ne urons, and thereby affects neural patterning.