CAMBRIDGE, Mass. (July 17, 2014) A signaling pathway once thought to have little if any role during embryogenesis is a key player in the formation of the front-most portion of developing vertebrate embryos. Moreover, signals emanating from this regionreferred to as the "extreme anterior domain" (EAD)orchestrate the complex choreography that gives rise to proper facial structure.
The surprising findings, reported by Whitehead Institute scientists this week in the journal Cell Reports, shed new light on a key process of vertebrate embryonic development.
"The results are exciting on a number of levels," says Whitehead Member Hazel Sive. "We uncovered two new and important things about facial formation, and it turns out they tie together."
Sive and her lab have long been using the frog Xenopus as a model in which to study development of the EAD into the mouth. Several years ago, Amanda Dickinson, a postdoctoral researcher at the time, and Sive showed that the Wnt signaling pathway, which is active throughout the body in a wide array of developmental processes and in cancer, is vital for mouth formation. At the time, they observed that frog embryos whose Wnt signaling was disrupted only in the EAD not only failed to develop mouths, but also experienced other facial abnormalities. This suggested that the EAD may act on adjacent regions as a craniofacial "organizer" or signaling center.
Intrigued by this possibility, the lab searched for regulatory factors in the EAD that could affect craniofacial formation as a whole. Microarray analysis pointed to three highly expressed genes that also happen to be active participants in the Kinin-Kallikrein signaling pathway, best known in humans for its roles in regulating blood pressure, inflammation, and kidney function.
"We had no inkling that this pathway was active in the embryo," says Sive.
The lab confirmed its findings through a series of loss-of-function (
|Contact: Matt Fearer|
Whitehead Institute for Biomedical Research