Sussman Caroline R, Vartanian Timothy, Miller Robert H
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4965, USA.
J Neurosci. 2005 Jun 15;25(24):5757-62. doi: 10.1523/JNEUROSCI.4748-04.2005.
Neuregulin is required for proper oligodendrocyte development, but which receptors are involved and whether neuregulin promotes or inhibits maturation remain controversial. To assess the roles of the neuregulin receptor ErbB4 in oligodendrocyte development, we examined oligodendrocyte initiation and maturation in cultures derived from erbB4 knock-out mice and rat spinal cord in the presence of neutralizing erbB4 antibodies. No differences in the development of O4+ oligodendrocytes were detected in the presence or absence of erbB4 signaling. All four epidermal growth factor receptor family members were detected in the ventral neural tube at approximately the time of initial oligodendrocyte development, consistent with redundancy in neuregulin receptor signaling at the onset of oligodendrocyte development. In contrast, greater numbers of differentiated (monoclonal antibody O1+) oligodendrocytes developed in neural tube explants from erbB4(-/-) mice than either erbB4(+/+) or erbB4(+/-) littermates as well as in cultures treated with anti-erbB4. These data indicate that ErbB4 is not required for oligodendrocyte development and, in fact, inhibits oligodendrocyte lineage maturation. Together with previous studies, these data suggest a model in which early oligodendrocyte lineage development is regulated by promiscuous neuregulin receptor signaling, but subsequent lineage progression occurs through a balance of receptor-specific promotion or inhibition of maturation.
神经调节蛋白是少突胶质细胞正常发育所必需的，但涉及哪些受体以及神经调节蛋白是促进还是抑制成熟仍存在争议。为了评估神经调节蛋白受体ErbB4在少突胶质细胞发育中的作用，我们在存在中和性ErbB4抗体的情况下，检查了源自erbB4基因敲除小鼠和大鼠脊髓的培养物中的少突胶质细胞起始和成熟情况。在有或没有ErbB4信号传导的情况下，未检测到O4 +少突胶质细胞发育的差异。在少突胶质细胞初始发育时，在腹侧神经管中检测到所有四种表皮生长因子受体家族成员，这与少突胶质细胞发育开始时神经调节蛋白受体信号传导的冗余性一致。相比之下，来自erbB4（-/-）小鼠的神经管外植体中发育出的分化（单克隆抗体O1 +）少突胶质细胞数量比erbB4（+/ +）或erbB4（+/-）同窝小鼠以及用抗ErbB4处理的培养物中的更多。这些数据表明，ErbB4不是少突胶质细胞发育所必需的，实际上，它会抑制少突胶质细胞谱系的成熟。与先前的研究一起，这些数据提出了一个模型，其中早期少突胶质细胞谱系发育受混杂的神经调节蛋白受体信号传导调节，但随后的谱系进展通过受体特异性促进或抑制成熟的平衡来发生。
