THE SLUG GENE IS NOT ESSENTIAL FOR MESODERM OR NEURAL CREST DEVELOPMENT IN MICE

The Slug gene encodes a zinc finger protein, homologous to the product of the Drosophila Snail gene, that is implicated in the generation an d migration of both mesoderm and neural crest cells in several vertebr ate species. We describe here the cloning and genetic analysis of the mouse Slug (Slugh) gene. Slugh encodes a 269-amino-acid protein that s hares 92% amino acid identity with the product of the chicken Slug gen e. We have characterized Slugh gene expression during early mouse embr yogenesis by whole mount in situ hybridization of Singh mRNA and throu gh detection of P-galactosidase expression from an in-frame Slugh(lacZ ) allele generated through homologous recombination. Singh 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 m igratory neural crest cells. Analysis of a targeted null mutation that deleted all Singh coding sequences revealed that Slugh is not require d for mesoderm formation or for neural crest generation, migration, or development in mice. These results indicate that neither the expressi on pattern nor the biological function of the Slug gene is conserved a mong all vertebrates. These data also raise interesting questions abou t the regulation of neural crest generation, which is one of the disti nguishing characteristics of the vertebrate subphylum. (C) 1998 Academ ic Press.