Aprocess as intricate as brain development requires precisely controlled expression of crucial genes, but it’s the different flavors of a protein, or isoforms, that the genes encode that do the heavy lifting.
“One thing that hadn’t been systematically studied is how those genes [involved in brain development] are spliced into different transcripts,” said Michael Gandal, a physician scientist at the University of Pennsylvania. “We think of genes as the main output of our genome, but they really aren’t. It’s the specific transcript of a gene and how it gets spliced together that ultimately is what makes a functional protein or a regulatory molecule.”
While researchers have shown how isoform diversity regulates synapse formation in the brain and contributes to the risk of developing neuropsychiatric disorders, less is known about their role in shaping neurodevelopment. Now, in a paper published in Science, Gandal and his team sequenced regions of the developing brain and discovered a number of different types of isoforms linked with neurodevelopmental disorders. These findings provide a framework that allows scientists to understand how isoforms and the way they change could potentially orchestrate and influence neurodevelopment.
“We were quite interested in understanding how genes regulate [development], how that process may go awry in individuals with neurodevelopmental disorders, and whether we can connect the two together through this study,” said Gandal.
Previous attempts to study isoforms in neurodevelopment used a technique called short-read sequencing. But this approach failed to provide a complete picture of the isoforms since they showed up as small fragments that the researchers had to stitch together into a meaningful picture. Gandal and his team bypassed this tedious task by using long-read sequencing, which gives researchers the ability to sequence entire, uninterrupted genetic sequences. With this approach, the researchers set out to get a better picture of the different isoforms during a critical window of development.
ByClaudia Lopez-Lloreda, PhD
Article can be accessed on: The Scientist