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
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.