Expression of a homologue 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 candidate tumor suppressor gene on the basis of frequent allelic loss and 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 sequences of XDCC alpha and human DCC are greater than 80% identical; each has four immunoglobulin-like domains, six fibronectin type III domains, and a cytoplasmic domain of about 325 amino acids. While RNase protection assays and immunoblotting studies failed to detect XDCC alpha expression in embryos prior to developmental stage 15, XDCC alpha expression was present in embryos from stages 19 to 46. Whole mount in situ hybridization studies localized XDCC alpha expression to developing forebrain, 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 DCC expression. These results indicate that XDCC alpha is developmentally regulated and expressed as a consequence of neural induction. Moreover, unlike some well-characterized tumor suppressor genes, such as the p53 and retinoblastoma genes, that are not differentially expressed in developing Xenopus embryos, the DCC gene may have a specific role in the morphogenesis of the brain and perhaps other tissues and organs.
Pierceall
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WE
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06536.
Reale
M A
MA
Candia
A F
AF
Wright
C V
CV
Cho
K R
KR
Fearon
E R
ER
D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003001:Cloning, Molecular; D000075389:DCC Receptor; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D016163:Genes, DCC; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D018076:DNA, Complementary; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins