PREDOMINANT EXPRESSION OF HUMAN ZIC IN CEREBELLAR GRANULE CELL LINEAGE AND MEDULLOBLASTOMA

Zic is a novel zinc finger protein which displays a highly restricted expression pattern in the adult and developing mouse cerebellum and is highly homologous to the recently cloned Drosophila pair-rule gene Op a. To clarify the mechanism for the development of the human cerebellu m and its involvement in human nervous system diseases, we have isolat ed human Zic cDNA and examined its expression by using monoclonal anti body against recombinant Zic protein. The nucleotide sequence of human Zic cDNA is 85% homologous to that of mouse Zic cDNA. Its putative am ino acid sequence is highly conserved (> 99%) except for substitution of only two amino acid residues. In situ chromosome hybridization loca lized the human Zic gene to chromosome band 3q24. Human Zic protein wa s immunohistochemically detected in the nuclei of the cerebellar granu le cell lineage from the progenitor cells of the external germinal lay er to the postmigrated cells of the internal granular layer. Furthermo re, Zic protein was detected in medulloblastoma (26/29 cases), whereas no other tumors examined (over 70 cases including primitive neuroecto dermal tumors) expressed this protein. These findings suggest that Zic is a potential biomarker for medulloblastoma as well as the human cer ebellar granule cell lineage.