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PMID: 11564761 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The erbB2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes.

The Journal of cell biology ·Vol. 154 ·No. 6 ·2001-09-17 ·Pages 1245-58

Park SK, Miller R, Krane I, Vartanian T

Abstract

Development of oligodendrocytes and the generation of myelin internodes within the spinal cord depends on regional signals derived from the notochord and axonally derived signals. Neuregulin 1 (NRG)-1, localized in the floor plate as well as in motor and sensory neurons, is necessary for normal oligodendrocyte development. Oligodendrocytes respond to NRGs by activating members of the erbB receptor tyrosine kinase family. Here, we show that erbB2 is not necessary for the early stages of oligodendrocyte precursor development, but is essential for proligodendroblasts to differentiate into galactosylcerebroside-positive (GalC+) oligodendrocytes. In the presence of erbB2, oligodendrocyte development is normal. In the absence of erbB2 (erbB2-/-), however, oligodendrocyte development is halted at the proligodendroblast stage with a >10-fold reduction in the number of GalC+ oligodendrocytes. ErbB2 appears to function in the transition of proligodendroblast to oligodendrocyte by transducing a terminal differentiation signal, since there is no evidence of increased oligodendrocyte death in the absence of erbB2. Furthermore, known survival signals for oligodendrocytes increase oligodendrocyte numbers in the presence of erbB2, but fail to do so in the absence of erbB2. Of the erbB2-/- oligodendrocytes that do differentiate, all fail to ensheath neurites. These data suggest that erbB2 is required for the terminal differentiation of oligodendrocytes and for development of myelin.

MeSH Terms
Animals Animals, Newborn Astrocytes/cytology,drug effects Cell Culture Techniques Cell Death/drug effects Cell Differentiation/genetics Cell Lineage/drug effects Embryo, Mammalian/cytology ErbB Receptors/metabolism Gene Expression Regulation, Developmental Mice Mice, Knockout Myelin Sheath/drug effects,metabolism,ultrastructure Neuregulins/pharmacology Neurites/drug effects Oligodendroglia/cytology,metabolism Receptor, ErbB-2/genetics,metabolism,physiology Receptor, ErbB-3/metabolism Receptor, ErbB-4 Signal Transduction Spinal Cord/cytology,embryology,growth & development
Chemicals
Neuregulins ErbB Receptors Erbb4 protein, mouse Receptor, ErbB-2 Receptor, ErbB-3 Receptor, ErbB-4
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Park S K
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Miller R
Krane I
Vartanian T
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200104025
Published
2001-09-17
Pages
1245-58
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2150828
Subset
IM
Grants
NINDS NIH HHS · P01 NS038475 · United States
NINDS NIH HHS · NS02028 · United States
NINDS NIH HHS · R01 NS030800 · United States
NINDS NIH HHS · NS30800 · United States
NINDS NIH HHS · P01 NS38475-01 · United States
External Links
PubMed source DOI: 10.1083/jcb.200104025 PMC Full Text View journal details
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