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Central nervous system myelination in mice with deficient expression of Notch1 receptor
Author(s) -
Givogri Maria I.,
Costa Rui M.,
Schonmann Vilma,
Silva Alcino J.,
Campagi Anthony T.,
Bongarzone Ernesto R.
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10128
Subject(s) - notch signaling pathway , myelin , biology , oligodendrocyte , central nervous system , microbiology and biotechnology , receptor , neuroscience , signal transduction , genetics
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. © 2002 Wiley‐Liss, Inc.