It's been over a year and a half since the landmark issue of the journal Development described nearly 2,000 new mutants of zebrafish (Danio rerio), the newest animal model of vertebrate development in a menagerie of such species. Now, developmental biologists all over the world are earnestly studying these mutants -- and adding new ones to the list -- to determine what role they play in complex biochemical pathways. As part of this effort, researchers at the University of Pennsylvania Medical Center have identified new mutants important in the first steps that control the dorsoventral -- back to abdomen -- arrangement of embryonic tissues, a process called patterning.
These genes guide embryonic cells to become the belly or the back of the developing fish, with mutations resulting in abnormally shaped embryos. Because many genetic guidance systems are generic, or conserved, across species -- from invertebrates to vertebrates -- understanding the biochemical nature of these abnormalities could point to similar anomalies that cause birth defects in humans and might shed light on what happens in human embryos in the mysterious first days after conception.
Mary C. Mullins, PhD, assistant professor of cell and development biology and one of the key authors in the 1996 zebrafish issue, studies dorsoventral patterning determined by the bone morphogenetic protein (bmp) signaling pathway, which has already been implicated in dorsoventral patterning in frogs. In humans, this pathway is involved in bone formation.
"Working with zebrafish has allowed us to study the in vivo function of this pathway, which isn't possible with frogs and mice," says Mullins. "The zebrafish mutants don't die as early as in the mouse, so we can study dorsoventral patterning in the zebrafish, which so far has not been possible in the mouse. This is important because this pathway sets up the body's future shape and organization."