Mutually Repulsive EphA7-EfnA5 Organize Region-to-Region Corticopontine Projection by Inhibiting Collateral Extension
Mutually Repulsive EphA7-EfnA5 Organize Region-to-Region Corticopontine Projection by Inhibiting Collateral Extension
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DOI：
10.1523/jneurosci.0367-20.2021
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发表时间：
2021-06-02
影响因子：
5.3
通讯作者：
Sato, Makoto
中科院分区：
文献类型：
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作者：
Iguchi, Tokuichi;Oka, Yuichiro;Sato, Makoto
熟练动作和运动规划的协调依赖于在胚胎发育期间连接皮层与皮层下区域的区域限制性脑回路的形成。第5层神经元分布在大多数皮质区域，通过侧支的突出和延伸，支配脑桥核（基底脑桥），侧支沿着它们的皮质脊髓延伸轴突延伸。已知脑桥衍生的趋化性线索吸引延伸的轴突，但尚未确定调节侧枝延伸以产生区域隔离的靶向模式的分子。在这里，我们发现EphA 7和EfnA 5以区域特异性和相互排斥的方式在皮质和基底脑桥中表达，并且它们的排斥活性对于分离小鼠皮质脊髓轴突束的侧支延伸至关重要。具体地，EphA7和EfnA5正向和反向抑制信号引导侧支延伸，使得EphA7阳性额叶和枕叶皮质区将其轴突侧支延伸到基底脑桥的EfnA5阴性吻侧部分中，而EfnA5阳性顶叶皮质区将其侧支延伸到基底脑桥的EphA7阴性尾侧部分中。总之，我们的研究结果提供了一个分子基础，解释了皮质桥脑投射如何将多模态皮质输出连接到其皮质下目标。
Coordination of skilled movements and motor planning relies on the formation of regionally restricted brain circuits that connect cortex with subcortical areas during embryonic development. Layer 5 neurons that are distributed across most cortical areas innervate the pontine nuclei (basilar pons) by protrusion and extension of collateral branches interstitially along their corticospinal extending axons. Pons-derived chemotropic cues are known to attract extending axons, but molecules that regulate collateral extension to create regionally segregated targeting patterns have not been identified. Here, we discovered that EphA7 and EfnA5 are expressed in the cortex and the basilar pons in a region-specific and mutually exclusive manner, and that their repulsive activities are essential for segregating collateral extensions from corticospinal axonal tracts in mice. Specifically, EphA7 and EfnA5 forward and reverse inhibitory signals direct collateral extension such that EphA7-positive frontal and occipital cortical areas extend their axon collaterals into the EfnA5-negative rostral part of the basilar pons, whereas EfnA5-positive parietal cortical areas extend their collaterals into the EphA7- negative caudal part of the basilar pons. Together, our results provide a molecular basis that explains how the corticopontine projection connects multimodal cortical outputs to their subcortical targets.