Bar Harbor, Maine--With names like Snail and Slug, you might expect genes belonging to the category known as the Snail family to be associated with some steady, slow-moving biological progression. Instead, these genes help direct the dynamic, fast-paced race of early embryonic development, when cells are dividing, migrating around the body and differentiating into the millions, even trillions, of specialized cells that constitute a mature organism.
Snail family genes are present in vertebrates and have counterparts in invertebrates such as the fruit fly Drosophila. To biologists, this means that these genes are "well conserved across species"--in other words, diverse species retained them as they evolved. So it's reasonable to expect that their function would be the same among all vertebrates: mice as well as frogs and birds, for instance.
In a paper just released in the Proceedings of the National Academy of Sciences, two Jackson Laboratory scientists have demonstrated both a confirmation of the consistent role of Snail genes in vertebrates, and a surprising exception.
Dr. Thomas Gridley and Dr. Steven Murray showed that Snail family genes operate consistently in mice and birds in controlling the acquisition of differences between the two sides of the body. While the body plan of all vertebrates is overtly symmetric on both body sides, most internal organs exhibit an asymmetric distribution. For example, in mammals the heart is located on the left side of the body while the liver is on the right. Gridley and Murray found that, similarly to what has been described for birds, the Snail gene controls acquisition of these asymmetric body differences in mice.
On the other hand, Gridley and Murray found that Snail family gene function relating to neural crest cells is different in mice. Neural crest cells are developmental cells that form at the border of the embryonic neural plate (a structure that later develops into the spinal cord and brain) during early embryo formation. In normal vertebrate development, these cells "delaminate," or separate, from the neural plate, migrate throughout the embryo, and differentiate at their final destinations into a wide variety of cell types.
In frog and bird embryos, Snail family genes are required for neural crest cell formation and delamination. Gridley and Murray discovered that mouse embryos lacking both Snail and Slug had severe defects, yet still formed neural crest cells that were able to delaminate and migrate.
"This work demonstrates that species-specific differences in the regulation of neural crest formation and migration are more profound than previously appreciated," said Gridley. "These results shed surprising new light on the roles of Snail family genes during early development in mammals, and the different roles these genes can play during evolution of individual vertebrate species."
The Jackson Laboratory is an independent, nonprofit research institution based in Bar Harbor, Maine, with facilities in West Sacramento, Calif. Its research staff of more than 450 investigates the genetic basis of cancers, heart disease, osteoporosis, Alzheimer's disease, glaucoma, diabetes, and many other human diseases and disorders, as well as normal mammalian development and bioinformatics. The Laboratory is also the world's source for nearly 3,000 strains of genetically defined mice, home of the Mouse Genome Database and many other publicly available information resources, and an international hub for scientific courses, conferences, training and education.
Journal
Proceedings of the National Academy of Sciences