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The vertebrate Unc5 genes, like their Caenorhabditis elegans counterpart, define a family of putative netrin receptors. One member of this family, Unc5h3, has been shown to have an important role during cell migration in the developing murine cerebellum. Mice homozygous for mutations in Unc5h3 are ataxic and have cerebellar hypoplasia and laminar structure defects. In addition, these mice have ectopic granule and Purkinje cells in the midbrain and brainstem. We have identified the human homologue of this gene, UNC5C, and shown it to have a restricted expression pattern in adult human tissues. By radiation hybrid analysis, we have determined that UNC5C localizes to chromosome 4q21-q23 between markers D4S1557 and D4S836 and is closely linked to the Parkinson disease gene.

Cerebellar deficient folia ( cdf ) is a recessive mouse mutation causing ataxia and cerebellar cytoarchitectural abnormalities, including hypoplasia, foliation defects, and Purkinje cell ectopia. To identify the cdf gene, we have generated a high-resolution genetic map of a 3.24 ± 0.55 cM (95% CI) region encompassing the cdf gene using 1997 F2 mice generated from a (C3H/HeSnJ- cdf/cdf × CAST/Ei)F1 intercross. Linkage analysis showed that the cdf gene cosegregates with D6Mit208, D6Mit359, and D6Mit225. A contig of five YACs, nine BACs, and three P1s was constructed across the cdf nonrecombinant region. Based on genetic and physical maps, the cdf gene was localized to the 0.28 ± 0.23 cM (95% CI) interval between D6Mit209 and D6Ack1. These results will greatly facilitate the map-based cloning of the cdf gene, which in turn should further knowledge of the molecular mechanisms of neuronal positioning and foliation during cerebellar development.