Development of the olivocerebellar projection.

Abstract

The establishment of orderly axonal projections is one of the essential steps in the formation of central networks. In this review, we discuss several of the current hypotheses on the mechanisms and molecules which govern this developmental process, using the olivocerebellar system as a model. During the formation of the olivocerebellar projection, there is a simultaneous and independent process of parcellation of the inferior olive and of the cerebellum. During embryogenesis, Purkinje cells in the cerebellar cortex and inferior olivary neurons are subdivided into small subsets of biochemically distinct compartments. We propose that this parcellation is involved in matching groups of olivary neurons to their corresponding subsets of target Purkinje cells. In vitro, the rotation of the anteroposterior axis of the cerebellum is followed by an equivalent inversion of the olivocerebellar projection. Olivary axons still project to the same Purkinje cells, suggesting that the formation of the olivocerebellar projection is regulated by positional information shared between pre- and postsynaptic neurons. We suggest that, in the chick embryo, the cell adhesion molecule BEN/SC1/DM-GRASP could be one of the target recognition molecules controlling the development of the olivocerebellar projection. These results also emphasize that coarse grained projection maps can form through chemoaffinity mechanisms, independent of the activity of the interacting neurons.