Developmental changes of glycosphingolipids and expression of glycogenes in mouse brains

Abstract

Glycosphingolipids (GSLs) and their sialic acid-containing derivatives, gangliosides, are important cellular components and are abundant in the nervous system. They are known to undergo dramatic changes during brain development. However, knowledge on the mechanisms underlying their qualitative and qualitative changes is still fragmentary. In this investigation, we have provided a detailed study on the developmental changes of the expression patterns of GSLs, GM3, GM1, GD3, GD1a, GD2, GD1b, GT1b, GQ1b, A2B5 antigens (c-series gangliosides such as GT3 and GQ1c), Chol-1a (GT1aa and GQ1ba), glucosylceramide, galactosylceramide (O1 antigen), sulfatide (O4 antigen), stage-specific embryonic antigen-1 (Lewis x) glycolipids, and human natural killer-1 glycolipid (sulfoglucuronosyl paragloboside) in developing mouse brains [embryonic day 12 (E12) to adult]. In E12-E14 brains, GD3 was a predominant ganglioside. After E16, the concentrations of GD3 and GM3 markedly decreased, and the concentrations of a-series gangliosides, such as GD1a, increased. GT3, glucosylceramide, and stagespecific embryonic antigen-1 were expressed in embryonic brains. Human natural killer-1 glycolipid was expressed transiently in embryonic brains. On the other hand, Chol-1a, galactosylceramide, and sulfatide were exclusively found after birth. To provide a better understanding of the metabolic basis for these changes, we analyzed glycogene expression patterns in the developing brains and found that GSL expression is regulated primarily by glycosyltransferases, and not by glycosidases. In parallel studies using primary neural precursor cells in culture as a tool for studying developmental events, dramatic changes in ganglioside and glycosyltransferase gene expression were also detected in neurons induced to differentiate from neural precursor cells, including the expression of GD3, followed by up-regulation of complex a-and b-series gangliosides. These changes in cell culture systems resemble that occurring in brain. We conclude that the dramatic changes in GSL pattern and content can serve as useful markers in neural development and that these changes are regulated primarily at the level of glycosyltransferase gene expression.

Neuromuscular synaptic transmission in aged ganglioside-deficient mice

“…Specific neuronal ganglioside levels vary during embryogenesis but also in postnatal phases, especially during ageing (Ando, 1983;Aydin et al, 2000;Malisan and Testi, 2002;Ngamukote et al, 2007;Svennerholm et al, 1989;Yamamoto et al, 2008). Gangliosides seem to become increasingly important upon ageing, as late-onset and progressive histological and behavioural abnormalities develop in both GM2/GD2-synthase knockout (GM2s-KO) mice and compound null-mutant mice lacking GM2/GD2-and GD3-synthase.…”

Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro

“…GD3 (CD60a), a b-series disialoganglioside, is known to be the dominant GSL species expressed in embryonic rodent brain, but its concentration rapidly decreases soon after birth (2). In adult mouse brain, GD3 was found to be primarily localized in the subventricular zone (SVZ) of the lateral ventricle, where NSCs robustly exist.…”

“…In early mammalian embryonic brain, the pattern of ganglioside expression is limited to simple gangliosides, predominantly GM3 (NeuAcα2-3Galβ1-4Glcβ1-1′Cer) and GD3 (NeuAcα2-8NeuAcα2-3Galβ1-4Glcβ1-1′Cer). In later developmental stages, however, more complex gangliosides prevail, particularly GM1 (Galβ1-3GalNAcβ1-4(NeuAcα2-3)Galβ1-4Glcβ1-1′Cer), GD1a (NeuAcα2-3Galβ1-3GalNAcβ1-4(NeuAcα2-3)Galβ1-4Glcβ1-1′ Cer), GD1b (Galβ1-3GalNAcβ1-4(NeuAcα2-8NeuAcα2-3) Galβ1-4Glcβ1-1′Cer), and GT1b (NeuAcα2-3Galβ1-3GalNAcβ1-4 (NeuAcα2-8NeuAcα2-3)Galβ1-4Glcβ1-1′Cer) (2,3). Because of the spatiotemporal expression patterns, gangliosides abundant in embryonic brain, such as GD3 and the c-series ganglioside antigen marker A2B5, have been considered to be useful stage-specific markers of early brain development (4,5).…”

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

“…Simple gangliosides (e.g. GM3 and GD3) are relatively abundant in early embryonic brain but decrease rapidly in later stages (Ngamukote et al, 2007).…”