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Research has been conducted on the role of the Notch4 gene in the intercellular signaling mechanism. The generation of the Notch4-deficient mice by gene targeting is described.

The mouse Nkx3.1 (ital) homeobox gene has roles in prostate development and in cancer. This gene is the earliest known marker of prostate epithelium in embryogenesis and is expressed after that at all stages of prostate differentiation in vivo and in tissue recombinants. NKX3.1 (ital) may be a prostate-specific tumor suppressor gene. Loss a single allele may constitute a predisposition to carcinogenesis in the prostate.

The Slug gene encodes a zinc finger protein, homologous to the product of the Drosophila Snail gene, that is implicated in the generation and migration of both mesoderm and neural crest cells in several vertebrate species. We describe here the cloning and genetic analysis of the mouse Slug (Slugh) gene. Slugh encodes a 269-amino-acid protein that shares 92% amino acid identity with the product of the chicken Slug gene. We have characterized Slugh gene expression during early mouse embryogenesis by whole mount in situ hybridization of Slugh mRNA and through detection of [Beta]-galactosidase expression from an in-frame [Slugh.sup.1acZ] allele generated through homologous recombination. Slugh expression is first detected in extraembryonic mesoderm and is later detected in many mesodermal subsets, although it is not detected in the primitive streak. In contrast to many other vertebrates, the mouse Slug gene is not expressed in premigratory neural crest cells but is expressed in migratory neural crest cells. Analysis of a targeted null mutation that deleted all Slugh coding sequences revealed that Slugh is not required for mesoderm formation or for neural crest generation, migration, or development in mice. These results indicate that neither the expression pattern nor the biological function of the Slug gene is conserved among all vertebrates. These data also raise interesting questions about the regulation of neural crest generation, which is one of the distinguishing characteristics of the vertebrate subphylum.

Byline: Rulang Jiang, Yu Lan, Christine R. Norton, John P. Sundberg, Thomas Gridley Abstract: The Slug gene encodes a zinc finger protein, homologous to the product of the Drosophila Snail gene, that is implicated in the generation and migration of both mesoderm and neural crest cells in several vertebrate species. We describe here the cloning and genetic analysis of the mouse Slug (Slugh) gene. Slugh encodes a 269-amino-acid protein that shares 92% amino acid identity with the product of the chicken Slug gene. We have characterized Slugh gene expression during early mouse embryogenesis by whole mount in situ hybridization of Slugh mRNA and through detection of [beta]-galactosidase expression from an in-frame Slugh.sup.lacZ allele generated through homologous recombination. Slugh expression is first detected in extraembryonic mesoderm and is later detected in many mesodermal subsets, although it is not detected in the primitive streak. In contrast to many other vertebrates, the mouse Slug gene is not expressed in premigratory neural crest cells but is expressed in migratory neural crest cells. Analysis of a targeted null mutation that deleted all Slugh coding sequences revealed that Slugh is not required for mesoderm formation or for neural crest generation, migration, or development in mice. These results indicate that neither the expression pattern nor the biological function of the Slug gene is conserved among all vertebrates. These data also raise interesting questions about the regulation of neural crest generation, which is one of the distinguishing characteristics of the vertebrate subphylum. Author Affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609

Jagged2 gene and Notch signaling, which is a intercellular signaling mechanism, play an important part in the limb, thymic and craniofacial development of mice. Mutant mice without a domain of the Jagged2 protein had fatal defects in craniofacial morphogenesis. The mice also had fusion in the limbs and modified thymic morphology.

The adhesive interactions between E-selectin lectin domain and the cell surface carbohydrate sialyl Lewis X (SLX) were investigated. E-selectin is a cell adhesion molecule that mediates cell adhesion by binding to SLX. The study protocol involved generating chimeric human-rabbit lectin domains and using these to map epitopes recognized by anti-E-selectin monoclonal antibodies (mAbs). Furthermore, functional residues identified from analyses of mutant E-selectin binding to anti-E-selectin mAbs were superimposed on a three-dimensional lectin model. The study identified a small region in the E-selectin lectin domain which is critical for SLX recognition.