Central nervous system myelination in mice with deficient expression of Notch1 receptor

J Neurosci Res. 2002 Feb 1;67(3):309-20. doi: 10.1002/jnr.10128.

Abstract

Activity of the Notch1 gene is known to inhibit oligodendrocyte (OL) differentiation in vitro. We tested the hypothesis that the Notch1 pathway regulates in vivo myelin formation, by examining brain myelination of Notch1 receptor null heterozygotes mutant animals (Notch1(+/-)). We show that a deficiency in Notch1 expression leads to increased abundance of products of specific myelin genes in myelinated areas of the brain during the first 2 weeks of postnatal life. We observed increased numbers of myelinated axons in optic nerves and the presence of myelinated fibers in the molecular layer (ML) of the Notch1(+/-) cerebella. These findings were accompanied by up-regulation of Mash1 and down-regulation of Hes5 proteins. In addition, we found expression of Jagged1, one of the Notch1 activators, in unmyelinated axons of the cerebellar ML during normal development. Our findings indicate that the Jagged/Notch signaling pathway might actively participate in the regulation of myelination during central nervous system development and suggest that certain neuronal populations might regulate whether their axons are myelinated by the expression of inhibitory signals such as Jagged1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / ultrastructure
  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • Cell Count
  • Cells, Cultured
  • Central Nervous System / cytology
  • Central Nervous System / metabolism*
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Heterozygote
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants
  • Myelin Sheath / metabolism*
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism
  • Optic Nerve / metabolism
  • Optic Nerve / ultrastructure
  • Protein Biosynthesis
  • Proteins*
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Receptor, Notch1
  • Receptors, Cell Surface*
  • Repressor Proteins / metabolism
  • Serrate-Jagged Proteins
  • Signal Transduction / physiology
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factors / metabolism

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Hes5 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Membrane Proteins
  • Notch1 protein, mouse
  • Proteins
  • RNA, Messenger
  • Receptor, Notch1
  • Receptors, Cell Surface
  • Repressor Proteins
  • Serrate-Jagged Proteins
  • Transcription Factors
  • HES5 protein, human