EXPRESSION OF A HOMOLOG OF THE DELETED IN COLORECTAL-CANCER (DCC) GENE IN THE NERVOUS-SYSTEM OF DEVELOPING XENOPUS EMBRYOS

The deleted in colorectal cancer (DCC) gene has been identified as a c andidate tumor suppressor gene on the basis of frequent allelic loss a nd decreased or absent gene expression in several human cancer types, as well as somatic mutations in the gene in colorectal tumors. We have identified a Xenopus DCC homologue (XDCC alpha) predicted to encode a protein of 1427 amino acids and have characterized XDCC expression in developing embryos and adult tissues. The predicted amino acid sequen ces of XDCC alpha and human DCC are greater than 80% identical; each h as four immunoglobulin-like domains, six fibronectin type III domains, and a cytoplasmic domain of about 325 amino acids. While RNase protec tion assays and immunoblotting studies failed to detect XDCC alpha exp ression in embryos prior to developmental stage 15, XDCC alpha express ion was present in embryos from stages 19 to 46. Whole mount in situ h ybridization studies localized XDCC alpha expression to developing for ebrain, midbrain, and hindbrain regions. DCC expression was inhibited by treatments that altered the development of mature neural structures ; specifically, uv-ventralized embryos and exogastrulae had reduced DC C expression. These results indicate that XDCC alpha is developmentall y regulated and expressed as a consequence of neural induction. Moreov er, unlike some well-characterized tumor suppressor genes, such as the p53 and retinoblastoma genes, that are not differentially expressed i n developing Xenopus embryos, the DCC gene may have a specific role in the morphogenesis of the brain and perhaps other tissues and organs. (C) 1994 Academic Press, Inc.