Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. In the brain cerebral cortex, loss of MGAT5 caused accelerated neuronal differentiation. Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development.
CITATION STYLE
Yale, A. R., Kim, E., Gutierrez, B., Hanamoto, J. N., Lav, N. S., Nourse, J. L., … Flanagan, L. A. (2023). Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. Stem Cell Reports, 18(6), 1340–1354. https://doi.org/10.1016/j.stemcr.2023.04.007
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