Jiang R, Lan Y, Norton C R, Sundberg J P, Gridley T
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Dev Biol. 1998 Jun 15;198(2):277-85.
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 the 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 SlughIacZ 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.
Slug基因编码一种锌指蛋白，与果蝇Snail基因的产物同源，在几种脊椎动物物种中，该基因与中胚层和神经嵴细胞的产生及迁移有关。我们在此描述小鼠Slug（Slugh）基因的克隆及遗传分析。Slugh编码一种由269个氨基酸组成的蛋白质，与鸡Slug基因的产物具有92%的氨基酸同一性。我们通过对Slugh mRNA进行全胚胎原位杂交以及检测通过同源重组产生的框内SlughIacZ等位基因的β-半乳糖苷酶表达，来表征小鼠早期胚胎发育过程中Slugh基因的表达情况。Slugh的表达首先在胚外中胚层中被检测到，随后在许多中胚层亚群中被检测到，不过在原条中未被检测到。与许多其他脊椎动物不同，小鼠Slug基因在迁移前的神经嵴细胞中不表达，但在迁移的神经嵴细胞中表达。对一个缺失了所有Slugh编码序列的靶向无效突变的分析表明，Slugh对于小鼠中胚层的形成或神经嵴的产生、迁移及发育并非必需。这些结果表明，Slug基因的表达模式和生物学功能在所有脊椎动物中并非都是保守的。这些数据也引发了关于神经嵴产生调控的有趣问题，神经嵴产生是脊椎动物亚门的显著特征之一。
