Gangliosides in Nerve Cell Specification

Research output: Chapter in Book/Report/Conference proceedingChapter

7 Scopus citations

Abstract

The central nervous system is generated from progenitor cells that are recognized as neural stem cells (NSCs). NSCs are defined as undifferentiated neural cells that are characterized by the capacity for self-renewal and multipotency. Throughout neural development, NSCs undergo proliferation, migration, and cellular differentiation, and dynamic changes are observed in the composition of carbohydrate-rich molecules, including gangliosides. Gangliosides are sialic acid-containing glycosphingolipids with essential and multifaceted functions in brain development and NSC maintenance, which reflects the complexity of brain development. Our group has pioneered research on the importance of gangliosides for growth factor receptor signaling and epigenetic regulation of ganglioside biosynthesis in NSCs. We found that GD3 is the predominant ganglioside species in NSCs (>80%) and modulates NSC proliferation by interacting with epidermal growth factor receptor signaling. In postnatal brain, GD3 is required for long-term maintenance of NSCs. Deficiency in GD3 leads to developmental and behavioral deficits, such as depression. The synthesis of GD3 is switched to the synthesis of complex, brain-type gangliosides, namely, GM1, GD1a, GD1b, and GT1b, resulting in terminal differentiation and loss of “stemness” of NSCs. In this process, GM1 is augmented by a novel GM1-modulated epigenetic gene regulation mechanism of glycosyltransferases at a later differentiation stage. Consequently, our research suggests that stage-specific gangliosides play specific roles in maintaining NSC activities and in cell fate determination.

Original languageEnglish (US)
Title of host publicationProgress in Molecular Biology and Translational Science
EditorsRonald L. Schnaar, Pablo H.H. Lopez
PublisherElsevier B.V.
Pages241-263
Number of pages23
ISBN (Print)9780128123416
DOIs
StatePublished - Jan 1 2018

Publication series

NameProgress in Molecular Biology and Translational Science
Volume156
ISSN (Print)1877-1173
ISSN (Electronic)1878-0814

Keywords

  • brain development
  • epigenetic regulation
  • epithelial growth factor receptor
  • growth factor
  • growth factor receptor
  • lipid raft
  • neural cell fate determination
  • neural progenitor cell
  • neural stem cell
  • neurogenesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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