The glycosylation enzyme MGAT5 plays a critical role in brain development, according to a study by UC Irvine researchers, a finding that may contribute to new therapeutic purposes for neural stem cells.
neurons and astrocytes oligodendrocyte They are the final mature cells of the brain and spinal cord made up of neural stem cells. Each has distinct and essential functions. Neurons transmit signals, astrocytes help modulate those signals, and oligodendrocytes prevent signals from deteriorating. When a cell makes proteins or lipids that end up on the surface of the cell, they often add small sugar molecules. The team tested whether this internal process – called glycosylation – affected how neural stem cells form mature brain cells.
The study published in the journal Stem Cell Reports, found that while glycosylation, MGAT5 enzyme significantly regulates the formation of neurons and astrocytes from neural stem cells. Neural stem cells without MGAT5 produce more neurons and fewer astrocytes during the very early stages of brain development, altering its structure. These changes may contribute to subsequent abnormal behavior patterns, including abnormal social interactions and repetitive actions.
Now that we know that MGAT5 and glycosylation have a significant impact on neurogenesis and astrocytes, we have a better idea of how our nervous system develops. We hope that these findings will contribute to the use of neural stem cells for therapeutic purposes by providing new information about the factors that regulate these cells.”
Lisa Flanagan, interview author, professor of neurology, UCLA School of Medicine
It was known that neural stem cells respond to external signals that they encounter during development. But it was not known whether neural stem cells could modulate their responses to these signals. The team analyzed the role of glycosylation enzymes in brain maturation by comparing control mice with those whose neural stem cells did not contain MGAT5. He found that neural stem cells use glycosylation to manage their interactions with external signals and to regulate the growth of mature brain cells.
“As we continue our work, we hope to identify which proteins and pathways on the cell surface that are controlled by glycosylation are essential for neurogenesis and astrocytes,” Flanagan said. “This will give us better insight into the extrinsic signals significantly modulated by glycosylation of neural stem cells, which in turn will help decipher the complex processes that occur during brain development and extend the therapeutic utility of neural stem cells.”
The team included researchers from the School of Medicine’s Departments of Anatomy, Neuroscience, Neuroscience, Neuroscience, and Laboratory Medicine as well as the Henry Samueli College’s Department of Biomedical Engineering and the Sue and Bill Gross Center for Stem Cell Research.
Yale, Arkansas, et al. (2023) Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. Stem Cell Reports. doi.org/10.1016/j.stemcr.2023.04.007.