Mechanisms of neural patterning and specification in the developing cerebellum.

Abstract

The cerebellar cortex is one of the best-studied regions of the CNS. For nearly a century, all of the cerebellar cell types and the patterns of their synaptic connections have been known. Much of this wealth of information comes from Ramon y Cajal's work (1889, 1911, 1960) with Golgi studies. Further infor­ mation on the development (Altman & Bayer 1985a-c, Rakic 1971, Miale & Sidman 1961), anatomy (Palay & Chan-Palay 1974), fiber tracts (BrodaI1981), and circuitry (Llinas & Hillman 1969) of the cerebellar cortex has emerged over the past several decades. The cerebellum provides a unique system for studying CNS development, combining the three classic patterns of CNS development-morphogenetic movements, the formation of ganglionic struc­ tures, and the establishment of neuronal layers-within one brain region. Remarkably simple in its basic plan, the adult cerebellar cortex contains only three layers and two principal classes of neurons. The abundance of one of these principal neurons, the granule cell, has enabled detailed analyses of the molecular mechanisms that underlie the basic steps in neuronal differentiation and has pointed out the role of local community factors in CNS neuronal development. Moreover, studies of naturally occurring mutations (Heintz et al 1993, Sidman 1968) and of targeted gene disruptions that block discrete steps in the development of this region (McMahon 1993, Joyner & Hanks 1991,