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

Citation
Sk. Park et al., The erbB2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes, J CELL BIOL, 154(6), 2001, pp. 1245-1258
Citations number
100
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
6
Year of publication
2001
Pages
1245 - 1258
Database
ISI
SICI code
0021-9525(20010917)154:6<1245:TEGIRF>2.0.ZU;2-J
Abstract
Development of oligodendrocytes and the generation of myelin internodes wit hin 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 olig odendrocyte development. Oligodendrocytes respond to NRGs by activating mem bers of the erbB receptor tyrosine kinase family. Here, we show that erbB2 is not necessary for the early stages of oligodendrocyte precursor developm ent, but is essential for proligodendroblasts to differentiate into galacto sylcerebroside-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 oligod endrocyte by transducing a terminal differentiation signal, since there is no evidence of increased oligodendrocyte death in the absence of erbB2. Fur thermore, known survival signals for oligodendrocytes increase oligodendroc yte numbers in the presence of erbB2, but fail to do so in the absence of e rbB2. Of the erbB2(-/-) oligodendrocytes that do differentiate, all fail to ensheath neurites. These data suggest that erbB2 is required for the termi nal differentiation of oligodendrocytes and for development of myelin.