The pharyngeal pouches develop the gills in fish, and in human fetuses they also form gill-like structures, which later organize the head skeleton and organs such as the thymus and thyroid. Birth defects like DiGeorge syndrome can be traced back to malformations in the development of the pharyngeal pouches, Crump said.
Choe developed more than 100 different transgenic lines, transferring key genes to live zebrafish embryos where they could be studied under the microscope at the single cell level. Surprisingly, the lengthy filming doesn't harm the embryos and they can grow up to be normal fish, Crump said.
The Wnt pathways are significant because they control two separate cell behaviors. Choe discovered this by finding a way to genetically block each pathway and then making time-lapse videos of how development went wrong in each case.
"In the future as we get better at harnessing stem cells to create organs, we hope to be able to bioengineer these cells to make a particularly shaped organ," Crump said. "What we're learning in zebrafish by studying these pouches will be generally applicable and we can pursue these basic principles to come up with new types of technology involving cellular therapy."
The team is now studying other signaling pathways and their possible contributions to organ development and defects.
|Contact: Leslie Ridgeway|
University of Southern California - Health Sciences