Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro
Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro
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DOI：
10.1523/jneurosci.21-13-04740.2001
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发表时间：
2001-07-01
影响因子：
5.3
通讯作者：
Dubois-Dalcq, M
中科院分区：
文献类型：
--
作者：
Calaora, V;Rogister, B;Dubois-Dalcq, M
神经调节蛋白1（Nrg-1）亚型已显示影响少突胶质细胞（CNS髓鞘形成细胞）的出现和生长。我们研究了ErbB受体的Nrg-1信号传导如何特异性地控制多能神经前体细胞（NP）产生少突胶质细胞的早期阶段。我们在这里表明，胚胎纹状体核蛋白表达多种Nrg-1转录本和蛋白质，以及它们的特异性受体，ErbB 2和ErbB 4，但不是ErbB 3。由纹状体NP合成的主要同种型是称为富含半胱氨酸结构域Nrg-1的跨膜III型同种型。为了检测Nrg-1的生物学效应，我们将可溶性ErbB 3（sErbB 3）添加到生长的神经球中。这种Nrg-1生物活性的抑制剂减少了NPs的有丝分裂并增加了它们的凋亡，导致神经球大小和数量的显着减少。当通过神经球粘附到基底上来诱导NP迁移和分化时，RT-PCR和Western印迹检测到的III型亚型水平下降，与分化中的星形胶质细胞、神经元和少突胶质细胞中Nrg-1荧光强度的下降平行。用sErbB 3预处理生长中的神经球诱导从神经球迁移出的NP产生的少突胶质细胞的比例增加了三倍。这种效应在不相关的可溶性受体中未观察到。在NP生长和分化过程中加入sErbB 3可增强少突胶质细胞的成熟，表现为半乳糖苷和髓鞘碱性蛋白的表达。我们建议，III型Nrg-1信号和可溶性ErbB受体调节少突胶质细胞从NP的发展。
Neuregulin 1 (Nrg-1) isoforms have been shown to influence the emergence and growth of oligodendrocytes, the CNS myelin-forming cells. We have investigated how Nrg-1 signaling of ErbB receptors specifically controls the early stages of oligodendrocyte generation from multipotential neural precursors (NPs). We show here that embryonic striatal NPs express multiple Nrg-1 transcripts and proteins as well as their specific receptors, ErbB2 and ErbB4, but not ErbB3. The major isoform synthesized by striatal NPs is a transmembrane type III isoform called cysteine-rich domain Nrg-1. To examine the biological effect of Nrg-1, we added soluble ErbB3 (sErbB3) to growing neurospheres. This inhibitor of Nrg-1 bioactivity decreased mitosis of NPs and increased their apoptosis, resulting in a significant reduction in neurosphere size and number. When NPs were induced to migrate and differentiate by adhesion of neurospheres to the substratum, the level of type III isoforms detected by RT-PCR and Western blot decreased in parallel with a reduction in Nrg-1 fluorescence intensity in differentiating astrocytes, neurons, and oligodendrocytes. Pretreatment of growing neurospheres with sErbB3 induced a threefold increase in the proportion of oligodendrocytes generated from NPs migrating out of the neurosphere. This effect was not observed with an unrelated soluble receptor. Addition of sErbB3 during NP growth and differentiation enhanced oligodendrocyte maturation as shown by expression of galactocerebroside and myelin basic protein. We propose that both type III Nrg-1 signaling and soluble ErbB receptors modulate oligodendrocyte development from NPs.