Chemokines are key regulators of migration in lymphoid tissues. In the thymus, maturing thymocytes move from the outer capsule to the inner medulla and thereby interact with different types of stromal cells that control their maturation and selection. In the process of searching for molecules specifically expressed at different stages of mouse thymic differentiation, we have characterized the cDNA coding for the thymus-expressed chemokine (TECK) and its receptor CCR9. The TECK receptor gene was isolated and shown to be localized on the mouse chromosome 9F1-F4. Thymic dendritic cells have been initially thought to be a prevalent source of TECK. In contrast, our results indicate that thymic epithelial cells constitute the predominant source of TECK. Consistent with the latter distribution, the TECK receptor is highly expressed by double-positive thymocytes, and TECK can chemoattract both double-positive and single-positive thymocytes. The TECK transcript is also abundantly expressed in the epithelial cells lining the small intestine. In conclusion, the interplay of TECK and its receptor CCR9 is likely to have a significant role in the recruitment of developing thymocytes to discrete compartments of the thymus.

Defining the molecular mechanisms involved in cancer formation and progression is still a major challenge in colorectal-cancer research. Our strategy was to characterize genes whose expression is altered during colorectal carcinogenesis. To this end, the phenotype of a colorectal tumour was previously established by partial sequencing of a large number of its transcripts and the genes of interest were selected by differential screening on high-density filters with mRNA of colorectal cancer and normal adjacent mucosa. Fifty-one clones were found over-expressed and 23 were underexpressed in the colorectal-cancer tissues of the 5 analyzed patients. Among the latter, clones 6G2 and 32D6 were found of particular interest, since they had significant homology with several homeodomain-containing genes. The highest degree of similarity was with the murine Cdx1 for 6G2, and with the murine Cdx2 and hamster Cdx3 for 32D6. Using a RT-PCR approach, complete sequence of both types of homeobox-containing cDNA was obtained. The amino-acid sequence of the human Cdx1 is 85% identical to the mouse protein, and human Cdx2 has 94% identity with the mouse Cdx2 and hamster Cdx3. Tissue-distribution analysis of Cdx1 and Cdx2 mRNA showed that both transcripts were specifically expressed in small intestine, in colon and rectum. Colorectal cancer is the second most common tumour in men and the third in women in the Western countries. Although much is known about the epidemiology, morphology and genetics of colorectal tumorigenesis, our knowledge of the perturbations of gene expression that occur in colorectal tumours remains limited. Such tumours may arise from benign adenomatous polyps, which later progress to adenocarcinomas through several molecular events. They thus provide a very useful paradigm for studying the molecular genetic bases of cancer. The multistep process leading to colorectal tumorigenesis probably involves the loss of function of tumour-suppressor genes, as well as the activation of oncogenes. Several important genes have already been identified, but they do not account for the whole process, and other genes are probably involved.Efforts have been made to characterize these genes. Differential hybridization techniques and screening of substracted libraries allowed the elucidation of some of them (Bartsch et al., 1986;Denis et al., 1993;Yow et al., 1988;Schweinfest et al., 1993;Kondoh et al., 1992; Barnard et al., 1992a, b). We developed an alternative strategy, in which the phenotype of a colorectal tumour was established by partial sequencing of a large number of randomly selected transcripts (Frigerio et al., 1995). This repertory of ESTs should therefore contain most of the differentially expressed genes. Recently, Nguyen et al. (1995) have developed an efficient method of differential screening in which cDNA clones are gridded on high-density colony filters and hybridized with complex probes derived from poly (A) 1 RNA from different cells or tissues. The signals observed are measured, providing a ''hybridization s...