A research team identifies a glycosylation enzyme that is important for brain development.

A study by researchers at the University of California, Irvine, found that the MGAT5 glycosylation enzyme is important for brain development. This could lead to new uses for neural stem cells in medicine.

The final mature cells of the brain and spinal cord that are produced by neural stem cells are oligodendrocytes, neurons, and astrocytes. Each has particular and key capabilities. Signals are sent by neurons, modified by astrocytes, and preserved by oligodendrocytes in the brain. Small sugar molecules are frequently added by cells when they make proteins or fats that end up on the cell surface. The team investigated whether this internal process, known as glycosylation, has an effect on the manner in which neural stem cells mature into mature brain cells.

The review, distributed in the diary Immature Microorganism Reports, found that during glycosylation, the MGAT5 catalyst altogether directs the arrangement of neurons and astrocytes in undifferentiated brain organisms. During the very early stages of brain development, neural stem cells lacking MGAT5 alter the structure of the brain by producing more neurons and fewer astrocytes. Later, abnormal behavior patterns, such as erratic social interactions and repetitive actions, may result from these changes.

“We now have a better understanding of how our nervous system develops since we now know that MGAT5 and glycosylation play a significant role in neuron and astrocyte creation. By revealing fresh knowledge regarding the elements regulating these cells, we anticipate that these discoveries will support the use of neural stem cells for therapeutic purposes.”

Lisa Flanagan, professor of neurology in UCI’s School of Medicine.

“Since we know MGAT5 and glycosylation significantly affect neuron and astrocyte arrangement, we have a superior idea of how our sensory system creates,” said relating creator Lisa Flanagan, teacher of nervous system science in UCI’s Institute of Medication. “By providing new information about the factors that regulate these cells, we hope these findings will contribute to the therapeutic use of neural stem cells.”

It was realized that undeveloped brain cells respond to the outside signals they experience during advancement. However, it wasn’t clear if neural stem cells could alter how they responded to those signals. By comparing control mice to those whose neural stem cells lacked the MGAT5 enzyme, the group investigated the role of glycosylation enzymes in brain maturation. It was discovered that glycosylation is used by neural stem cells to control their responses to external signals and the development of mature brain cells.

Flanagan stated, “We hope to determine which cell surface proteins and pathways controlled by glycosylation are critical for the formation of neurons and astrocytes.” Because of this, we will have a better understanding of the external signals that are significantly altered by the glycosylation of neural stem cells. This will help us unravel the intricate processes that take place during brain development and increase the therapeutic potential of neural stem cells.”

Researchers from the Sue and Bill Gross Stem Cell Research Center, the Henry Samueli School of Engineering’s Department of Biomedical Engineering, and the School of Medicine’s departments of anatomy and neurobiology, neurology, and pathology and laboratory medicine were on the team.

More information: Andrew R. Yale et al, Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation, Stem Cell Reports (2023). DOI: 10.1016/j.stemcr.2023.04.007

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