How cells shape complex tissues and organs during embryonic development, which makes us who we are, holds many mysteries.
New research from the University of Cincinnati has examined such a process that leads to the formation of the spine or spine. If this process is disrupted, a birth defect called congenital scoliosis, or curvature of the spine, results. UC research has not only advanced the understanding of complex biological tissue formation, but it may also lead to possible treatments for scoliosis in the future.
The research was published in the journal Nature.
“We are studying a fundamental scientific problem, the formation of the spine, the spinal backbone that we all have,” says Ertuğrul Özbudak, PhD, professor in the Department of Pediatrics in the Division of Developmental Biology at UC College of Medicine as well as Cincinnati Children’s Hospital Medical Center and lead author of the study. “By uncovering the central mechanism that governs it, we are able to rearrange this mechanism in the mutant zebrafish that normally lacks this process.”
Özbudak says that in all vertebrate species, including humans, the vertebral column is made up of segmented vertebral discs. These discs that form the spine come from embryonic segments called somites. As the body of the embryo elongates in all vertebrate species, it is cut into somites by a “biological clock knife”.
“As humans, we all go through this knife-cutting process through clock genes that express themselves as blades,” says Özbudak. “There is a biological clock that controls this. Each time this clock ticks, the knife descends and then separates the disc’s precursors, the somites, from others that will form later.
“Certain genes are part of this clock. When they are moved, it leads to scoliosis because there is no longer a knife that cuts,” he adds. “By discovering this unknown hierarchy and mimicking it with pharmaceutical drugs, we are now able to restore and rearrange this missing segmentation in mutants that miss the molecular clock.”
Özbudak says the four UC students worked on the project and all contributed in different ways, bringing different skills and talents to the research. Chandel Angad Singh, a second-year doctoral student in the Systems Physiology graduate program, designed a genetically modified animal model while Didar Saparov, a third-year doctoral student in the Molecular Biology graduate program and development at Cincinnati Children’s Hospital, conducted experiments with pharmaceutical drugs. Oriana Zinani, now a Ph.D. from the Molecular and Developmental Biology program, verified the accuracy of a genetic reporter fish for the molecular clock. Nick Clason, as an undergraduate cooperative intern in the Department of Computer Science, contributed to the molecular simulations involved in the study.
“They had different backgrounds as undergraduates and they all did research in my lab,” Özbudak says of the students. “They formed a great multidisciplinary team. In their license [studies] Didar, Angad and Oriana specialized in physics, biomedical engineering and biology respectively. The team is led by Dr. Muhammed Simsek, a senior postdoctoral researcher in my lab at Cincinnati Children’s Hospital. »
Özbudak says the publication of the research triggered positive responses from other scientists internationally.
“They find this study important and groundbreaking. We hope it will energize not only our lab members working on this project, but also several labs around the world,” he said. “In a globalized society, I hope that everyone will participate equally, and that researchers from different countries and from different universities will take these results and take them forward.
“Collectively, we will better understand why certain mutations cause disease and we will understand the mechanisms behind them, which will one day be useful in curing congenital scoliosis.
