The erbB2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes.
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.
Park
S K
SK
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Miller
R
R
Krane
I
I
Vartanian
T
T
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology; D066246:ErbB Receptors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D020880:Neuregulins / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D020893:Receptor, ErbB-3 / Q000378:metabolism; D066247:Receptor, ErbB-4; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology / Q000254:growth & development
D066246:ErbB Receptors; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587690:Erbb4 protein, mouse