The small GTPase RhoA is required for proper locomotor circuit assembly.
The small GTPase RhoA is required for proper locomotor circuit assembly.
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DOI：
10.1371/journal.pone.0067015
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tolias KF
中科院分区：
文献类型：
--
作者：
Mulherkar S;Liu F;Chen Q;Narayanan A;Couvillon AD;Shine HD;Tolias KF
发育过程中神经元回路的组装需要轴突的精确导航，这是由吸引和排斥的引导线索控制的。在发育中的脊髓中，ephrinB3作为一种短程排斥性信号，阻止表达EphA4受体的皮质脊髓束和脊髓中间神经元轴突穿过中线，确保运动回路的正确形成。在这里，我们报告说，小GTHBRRhoA，细胞骨架动力学的关键调节，也需要ephrinB3/EphA4依赖的运动回路的形成。从神经祖细胞中删除RhoA导致小鼠表现出兔样跳跃步态，这与缺乏ephrinB3或EphA4的小鼠表型相似。与这种运动缺陷一致，我们发现RhoA缺陷小鼠的皮质脊髓束轴突和脊髓中间神经元投射异常地穿过脊髓中线。此外，我们确定RhoA的丢失阻断了ephrinB3诱导的皮质轴突生长锥塌陷，并破坏了ephrinB3在脊髓中线的表达。总的来说，我们的研究结果表明，RhoA是必不可少的ephrinB3/EphA4依赖组件的皮质和脊髓运动电路，控制正常的运动行为。
The assembly of neuronal circuits during development requires the precise navigation of axons, which is controlled by attractive and repulsive guidance cues. In the developing spinal cord, ephrinB3 functions as a short-range repulsive cue that prevents EphA4 receptor-expressing corticospinal tract and spinal interneuron axons from crossing the midline, ensuring proper formation of locomotor circuits. Here we report that the small GTPase RhoA, a key regulator of cytoskeletal dynamics, is also required for ephrinB3/EphA4-dependent locomotor circuit formation. Deletion of RhoA from neural progenitor cells results in mice that exhibit a rabbit-like hopping gait, which phenocopies mice lacking ephrinB3 or EphA4. Consistent with this locomotor defect, we found that corticospinal tract axons and spinal interneuron projections from RhoA-deficient mice aberrantly cross the spinal cord midline. Furthermore, we determined that loss of RhoA blocks ephrinB3-induced growth cone collapse of cortical axons and disrupts ephrinB3 expression at the spinal cord midline. Collectively, our results demonstrate that RhoA is essential for the ephrinB3/EphA4-dependent assembly of cortical and spinal motor circuits that control normal locomotor behavior.
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