First Author | Yale AR | Year | 2023 |
Journal | Stem Cell Reports | Volume | 18 |
Issue | 6 | Pages | 1340-1354 |
PubMed ID | 37172586 | Mgi Jnum | J:336895 |
Mgi Id | MGI:7492923 | Doi | 10.1016/j.stemcr.2023.04.007 |
Citation | Yale AR, et al. (2023) Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation. Stem Cell Reports 18(6):1340-1354 |
abstractText | 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 beta1,6-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. |