MOUSE ZIC1 IS INVOLVED IN CEREBELLAR DEVELOPMENT

Zic genes encode zinc finger proteins, the expression of which is high ly restricted to cerebellar granule cells and their precursors. These genes are homologs of the Drosophila pair-rule gene odd-paired. To cla rify the role of the Zic1 gene, we have generated mice deficient in Zi c1. Homozygous mice showed remarkable ataxia during postnatal developm ent. Nearly all of the mice died within 1 month. Their cerebella were hypoplastic and missing a lobule in the anterior robe. A bromodeoxyuri dine labeling study indicated a reduction both in the proliferating ce ll fraction in the external germinal layer (EGL), from 14 d postcoitum , and in forward movement of the EGL. These findings suggest that Zic1 may determine the cerebellar folial pattern principally via regulatio n of cell proliferation in the EGL.