MATH1 IS ESSENTIAL FOR GENESIS OF CEREBELLAR GRANULE NEURONS

The cerebellum is essential for fine motor control of movement and pos ture, and its dysfunction disrupts balance and impairs control of spee ch, limb and eye movements. The developing cerebellum consists mainly of three types of neuronal cells: granule cells in the external germin al layer, Purkinje cells, and neurons of the deep nuclei(1). The molec ular mechanisms that underlie the specific determination and the diffe rentiation of each of these neuronal subtypes are unknown. Math1 (refs 2, 3), the mouse homologue of the Drosophila gene atonal(4), encodes a basic helix-loop-helix transcription factor that is specifically exp ressed in the precursors of the external germinal layer and their deri vatives. Here we report that mice lacking Math1 fail to form granule c ells and are born with a cerebellum that is devoid of an external germ inal layer. To our knowledge, Math1 is the first gene to be shown to b e required in vivo for the genesis of granule cells, and hence the pre dominant neuronal population in the cerebellum.