UC research group utilizes zebrafish to contemplate a quality change that causes intrinsic scoliosis

UC research group utilizes zebrafish to contemplate a quality change that causes intrinsic scoliosis


  • Post By : Kumar Jeetendra

  • Source: University of Cincinnati

  • Date: 24 Jan,2021

Popular in aquariums throughout the world, the zebrafish is native to South Asia. But here in a Cincinnati Children’s laboratory, the freshwater variant plays a vital role in scientific discovery.

The patterning of the zebrafish’s spine gives the appearance of stripes; it is controlled by segmentation genes which function as a clock.

Zinani is part of a group of scientists in the laboratory of Ertuğrul M. Özbudak, PhD, associate professor of pediatrics at UC and Cincinnati Children’s Hospital Medical Center. Zebrafish eggs are fertilized and develop beyond their mother’s body which makes visualization with high resolution imaging simpler for researchers. Zebrafish and people share 70% of the same genes.

We can see exactly what’s happening while it’s happening in zebrafish providing us with insight for human embryonic development. My research asks the question, ‘How does the zebrafish embryo robustly achieve precise development in a variety of environments that consider variables such as temperature fluctuations and exposure to different oxygenation levels?’ We realized that embryos need to develop mechanisms to filter out the noise for development, and I focus on what those mechanisms involve.”

Oriana Zinani, Doctoral Student, University of Cincinnati College of Medicine

Scientists for a while have known that specific genes pair up on the same chromosome and appear together or”co-express” in cells and tissues. In humans, at least 10% of genes pair on the same chromosome. Why this happens has been unknown but the team — including Zinani, Özbudak, Kemal Kesero?lu, a research fellow at Cincinnati Children’s, and Ahmet Ay of Colgate University — did an experiment separating two genes that were paired together to determine the role they may play in spinal column development.

The team’s findings were recently published in the scholarly journal Nature.

Using the gene-editing instrument CRISPR-Cas9, the research team conducted a simple experiment using a zebrafish model and separated two enzymes that pair up to restrain the healthy development of the spine. The genes that are separated have broken their co-expression. Rather than the precise segment boundaries we’re accustomed to seeing in zebrafish embryos, we see instead a fused tissue, which ultimately leads to failed vertebrae formation.

“With two paired operational genes we see regular healthy development,” says Zinani. “If this were a person the individual would have no disease. If we take the standard gene pairs and separate them, without producing any mutation at all, we see disease development under environmental stress.”

Pictures of a zebrafish with the separated genes show a jagged vertebrae that’s broken, chipped and fused, explains Zinani. The zebrafish has a diseased phenotype leading to congenital scoliosis. Researchers also raised the zebrafish with separated gene pairs in various temperatures to better understand the effect of environmental stress on development. Paired genes contribute to beneficial spinal growth, particularly under environmental stress.

“What is also exciting is many genes responsible for the development of diabetes, cancer and autoimmune disorders also present in gene pairs in human genome” says Zinani. “We believe more research will reveal the significance of those genes maintaining close proximity to their partners. If the process of getting genes next to each other influences healthy development and adult life, we have a new target to consider in analyzing disease formation.”

Özbudak said Zinani’s work will be useful in future research.

“What Oriana found during her graduate study could shed light on why cows maintain particular gene orders in their genome: to coordinate expression of genes working in same biological processes,” he said.

Journal reference:

Zinani, O.Q.H., et al. (2021) Pairing of segmentation clock genes drives robust pattern formation. Nature. doi.org/10.1038/s41586-020-03055-0.

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