New study focuses on proteins' role in embryonic development

The new article from the lab of Theodora Koromila, assistant professor of biology at The University of Texas at Arlington, focuses on the proteins Odd-paired (Opa) and Ocelliless (Oc), and their dynamic roles in embryonic head development. 

In most animals, the process of development begins with fertilization, followed by the blastula stage, during which the embryo becomes a one-dimensional layer of epithelial cells, which make up primary tissues throughout the body. Koromila noted that her lab uses the fruit fly (Drosophila melanogaster) embryo because it develops very quickly and about 75 percent of human disease genes have a recognizable match in fruit flies. 

In the fly embryo, in addition to Opa and Oc, the proteins Zelda and Bicoid play important roles in embryonic development. Zelda appears to be a master regulator of genome activation in the earliest stages of the process, while Bicoid serves to organize the anterior body pattern. The UTA team in collaboration with the Bioinformatics

Resource Center at the Beckman lnstitute of Caltech, found that the balance between Opa and Oc is important in regulating the timing of gene expression before the embryo separates into distinct, individual cells.

“The main interest in my lab is understanding the basic mechanisms of cell differentiation—how do cells at these early embryonic stages express genes differently over time and become part of different tissues and different organs?” Koromila said. “Imagine the Drosophila embryo is like an orchestra, and the musicians are the cells: all the cells have the same DNA but they expressed differently over time. Similar to an orchestra, all the musicians have the same score but each one of them plays their own part. 

“Each one of these cells expresses specific genes at specific times in specific locations, because those genes will help specific cells to become part of the brain, part of the eyes, and so on.”

For this research, Kelli Fenelon, postdoctoral research associate in Koromila’s lab, used super-resolution microscopy in which he was able to image gene expression in individual cells. The team discovered that Opa’s and Oc’s overlapping expression domains are dynamic in the head region, with both being simultaneously transcribed at the blastula stage. They demonstrated a short (less than an hour) overlap in Opa and Oc expression in cells likely destined for brain development before the onset of gastrulation. 

“We didn’t know that before,” Koromila said. “There’s a known role for Oc in head development, but nobody thought that Opa would have a role in brain development. When Kelli saw this overlap between the two proteins, we thought this was very interesting and wanted to explore more.”

Fenelon said that the team’s findings include evidence that brain development, specifically, begins earlier than previously assumed.

“Even before the germ layers are formed at gastrulation, there is a stem cell niche which seems likely to be the brain primordium,” he said. “Among the intriguing findings from the study, there seems to be a changing relationship between Oc and Zelda, particularly relating to co-occupancy proximity to gene loci, as the embryo transitions into gastrulation, indicating a rich potential for future study.”

The team plans to do more experiments to better understand the role of the Opa and Oc proteins in brain development. “Understanding head development in the fly embryo will hopefully help us appreciate how brain development happens in human embryos,” Koromila said.