Because the expression of two of the pathway genes yields the peptide Bradykinin, the researchers theorized that introducing Bradykinin into LOF embryos at the appropriate stage would allow them to develop normally. They implanted tiny beads soaked with Bradykinin peptides, rescuing not only mouth formation but also proper neural crest development. The Kinin-Kallikrein pathway ultimately produces the signaling molecule nitric oxide (NO). Not surprisingly, the scientists found reduced NO levels in their LOF embryos. As they predicted, peptide-soaked beads led to an increase in NO production, further confirming the role of the pathway and its genes during facial formation. Importantly, NO had not been thought critical for development of this region.
Finally, in an effort to determine whether the requirement for Kinin-Kallikrein signaling in craniofacial development is conserved, Sive lab graduate student Justin Chen turned to LOF experiments in zebrafish. They found one of the pathway genes to be necessary for proper formation of both the mouth and the neural crest.
"This study greatly enhances our overall view of craniofacial development," says Laura Jacox, a graduate student pursuing a dual DMD-PhD degree through the Harvard School of Dental Medicine and the Harvard-MIT Health Sciences and Technology program. "Knowing what tissues are communicating with each other may help us determine where we could intervene to prevent or treat developmental abnormalities of the face."
Jacox is co-
|Contact: Matt Fearer|
Whitehead Institute for Biomedical Research