Ephrin-A5 exerts positive or inhibitory effects on distinct subsets of EphA4-positive motor neurons
Ephrin-A5 exerts positive or inhibitory effects on distinct subsets of EphA4-positive motor neurons
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DOI：
10.1523/jneurosci.4719-03.2004
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发表时间：
2004-02-04
影响因子：
5.3
通讯作者：
Krull, CE
中科院分区：
文献类型：
--
作者：
Eberhart, J;Barr, J;Krull, CE
在发育中的神经系统中，Eph受体酪氨酸激酶和肝配蛋白是轴突形成和可塑性所必需的。通常，Eph-ephrin相互作用促进抑制事件;例如，禁止神经细胞进入某些胚胎领域。在这里，我们表明，表达EphA 4的运动神经元的不同子集对ephrin-A5的反应不同。EphA 4阳性LMC（I）轴突避免进入肝配蛋白-A5阳性后肢中胚层。相比之下，EphA 4阳性MMC（m）轴突延伸通过肝配蛋白-A5阳性喙侧半硬结。阻断MMC（m）神经元中的EphA 4活化或扩大体节中ephrin-A5表达的结构域导致MMC（m）轴突异常生长到尾侧半硬结中。此外，MMC（m）神经元中EphA 4的过早表达导致其轴突的一部分生长成新的肝配蛋白-A5阳性区域。总之，这些结果表明EphA 4-肝配蛋白-A5信号传导以积极的方式作用以将MMC（m）轴突约束到喙侧半硬结。此外，我们表明Eph激活定位于LMC（I）和MMC（m）神经元的不同亚细胞区室，与这些神经元亚群中不同的EphA 4信号级联一致。
Eph receptor tyrosine kinases and ephrins are required for axon patterning and plasticity in the developing nervous system. Typically, Eph-ephrin interactions promote inhibitory events; for example, prohibiting the entry of neural cells into certain embryonic territories. Here, we show that distinct subsets of motor neurons that express EphA4 respond differently to ephrin-A5. EphA4-positive LMC(l) axons avoid entering ephrin-A5-positive hindlimb mesoderm. In contrast, EphA4-positive MMC(m) axons extend through ephrin-A5-positive rostral half-sclerotome. Blocking EphA4 activation in MMC(m) neurons or expanding the domain of ephrin-A5 expression in the somite results in the aberrant growth of MMC( m) axons into the caudal half-sclerotome. Moreover, premature expression of EphA4 in MMC(m) neurons leads to a portion of their axons growing into novel ephrin-A5-positive territories. Together, these results indicate that EphA4-ephrin-A5 signaling acts in a positive manner to constrain MMC(m) axons to the rostral half-sclerotome. Furthermore, we show that Eph activation localizes to distinct subcellular compartments of LMC(l) and MMC(m) neurons, consistent with distinct EphA4 signaling cascades in these neuronal subpopulations.