Live embryo images hint at birth defect origins

USC (US) — Scientists have used time-lapse photography to discover clues about the development of the head at the cellular level, which could lead to a better understanding of how organs and birth defects form in people.

The new study shows the role of two important molecular signaling pathways that help control the number and position of repeated units of cells that pattern the head and face.

Two members of a “Wnt” signaling pathway are instrumental in forming pharyngeal pouches that organize the structure of the head and face. Problems with forming the pouches can result in birth defects, including the rare DiGeorge syndrome, which causes an array of symptoms including an abnormal facial appearance, cleft palate, congenital heart disease, and loss of the thyroid and thymus.



Published in the journal Developmental Cell, the five years of research involved photographing live zebrafish embryos every 10 minutes for 36-hour periods with a sophisticated microscope, which enabled the researchers to see the pouches forming in real time.

“Zebrafish and humans are similar at the genetic level and the organ level,” says Gage Crump, assistant professor in cell and neurobiology at the University of Southern California (USC) and corresponding author on the research. “They have almost all the same organs that we do, which makes the fish a very relevant system for understanding human health and disease.”

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 says.

The study’s principal author Chong Pyo 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 says.

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 says.

“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.

Researchers from California Institute of Technology (Caltech) and the Fred Hutchinson Cancer Research Center contributed to the study that was funded by the California Institute for Regenerative Medicine (CIRM).

Source: USC