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The Snail gene family encodes zinc finger-containing transcriptional repressor proteins. Three members of the Snail gene family have been described in mammals, encoded by the Snai1, Snai2, and Snai3 genes. The function of the Snai1 and Snai2 genes have been studied extensively during both vertebrate embryogenesis and tumor progression and metastasis, and play critically important roles during these processes. However, little is known about the function of the Snai3 gene and protein. We describe here generation and analysis of Snai3 conditional and null mutant mice. We also generated an EYFP-tagged Snai3 null allele that accurately reflects endogenous Snai3 gene expression, with the highest levels of expression detected in thymus and skeletal muscle. Snai3 null mutant homozygous mice are viable and fertile, and exhibit no obvious phenotypic defects. These results demonstrate that Snai3 gene function is not essential for embryogenesis in mice. [ABSTRACT FROM AUTHOR]

The sensory epithelium within the mammalian cochlea (the organ of Corti) is a strictly ordered cellular array consisting of sensory hair cells and nonsensory supporting cells. Previous research has demonstrated that Notch-mediated lateral inhibition plays a key role in the determination of cell types within this array. Specifically, genetic deletion of the Notch ligand, Jagged2, results in a significant increase in the number of hair cells that develop within the sensory epithelium, presumably as a result of a decrease in Notch activation. In contrast, the downstream mediators and targets of the Notch pathway in the inner ear have not been determined but they may include genes encoding the proneural gene Math1 as well as the HES family of inhibitory bHLH proteins. To determine the potential roles of these genes in cochlear development, in situ hybridization for Math1 and HES5 was performed on the cochleae of wildtype vs. Jagged2 mutants ( Jag2 ΔDSL ). Results in wild-type cochleae show that expression of Math1 transcripts in the duct begins on E13 and ultimately becomes restricted to hair cells in the sensory epithelium. In contrast, expression of HES5 begins on E15 and becomes restricted to supporting cells in the epithelium. Results in Jag2 mutant cochleae suggest that Math1 transcripts are ultimately maintained in a larger number of cells as compared with wildtype, while transcripts for HES5 are dramatically reduced throughout the epithelium. These results are consistent with the hypothesis that activation of Notch via Jagged2 acts to inhibit expression of Math1 in cochlear progenitor cells, possibly through the activity of HES5. [ABSTRACT FROM AUTHOR]

The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism essential for embryonic development in mammals. Mutations in the human JAGGED1 (JAG1) gene, which encodes a ligand for the Notch family of transmembrane receptors, cause the autosomal dominant disorder Alagille syndrome. We have examined the in vivo role of the mouse Jag1 gene by creating a null allele through gene targeting. Mice homozygous for the Jag1 mutation die from hemorrhage early during embryogenesis, exhibiting defects in remodeling of the embryonic and yolk sac vasculature. We mapped the Jag1 gene to mouse chromosome 2, in the vicinity of the Coloboma (Cm) deletion. Molecular and complementation analyses revealed that the Jag1 gene is functionally deleted in the Cm mutant allele. Mice heterozygous for the null Jag1 allele exhibit an eye dysmorphology similar to that of Cm[sup /+] heterozygotes, but do not exhibit other phenotypes characteristic of Cm[sup /+] mice or of humans with Alagille syndrome. These results establish the phenotype of Cm[sup /+] mice as a contiguous gene deletion syndrome and demonstrate that Jag1 is essential for remodeling of the embryonic vasculature. [ABSTRACT FROM AUTHOR]