Protocadherin-18b interacts with Nap1 to control motor axon growth and arborization in zebrafish.
Protocadherin-18b interacts with Nap1 to control motor axon growth and arborization in zebrafish.
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DOI：
10.1091/mbc.e13-08-0475
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发表时间：
2014-03
影响因子：
3.3
通讯作者：
Jontes JD
中科院分区：
文献类型：
--
作者：
Biswas S;Emond MR;Duy PQ;Hao le T;Beattie CE;Jontes JD
干扰Pcdh18b功能导致发育中的斑马鱼运动轴突枝状化受损。Pcdh18b与肌动蛋白组装调节因子NAP1相互作用。时间推移成像显示Pcdh18b和NAP1可能通过调节轴突丝足的密度而影响轴突的树枝形成。发育过程中神经回路的正确组装需要精确控制轴突的生长、引导和树枝形成。尽管细胞表面受体的原钙粘附素家族被广泛假设参与神经回路组装，但它们在神经元发育中的具体作用仍然很大程度上是未知的。在这里，我们证明斑马鱼pcdh18b参与调节初级运动神经元的轴突树枝形成。虽然轴突的生长和延长看起来是正常的，但反义吗啡敲除pcdh18b会导致尾侧初级运动神经元中的轴突分支缺陷，这是剂量依赖性的。细胞移植实验表明，这种作用是细胞自主的。Pcdh18b通过其胞内结构域与WAVE复合体的核心成分NAP1相互作用，提示其在肌动蛋白组装的控制中发挥作用。与Pcdh18b一样，NAP1的缺失会导致运动轴突分支的减少。时间推移成像和轴突动力学的定量分析表明，Pcdh18b和NAP1都通过影响沿着延伸轴突轴突的丝状足的密度来调节轴突的分枝。
Interference with Pcdh18b function results in impaired arborization of motor axons in the developing zebrafish. Pcdh18b interacts with Nap1, a regulator of actin assembly. Time-lapse imaging indicates that both Pcdh18b and Nap1 may affect axon arborization by regulating the density of axonal filopodia. The proper assembly of neural circuits during development requires the precise control of axon outgrowth, guidance, and arborization. Although the protocadherin family of cell surface receptors is widely hypothesized to participate in neural circuit assembly, their specific roles in neuronal development remain largely unknown. Here we demonstrate that zebrafish pcdh18b is involved in regulating axon arborization in primary motoneurons. Although axon outgrowth and elongation appear normal, antisense morpholino knockdown of pcdh18b results in dose-dependent axon branching defects in caudal primary motoneurons. Cell transplantation experiments show that this effect is cell autonomous. Pcdh18b interacts with Nap1, a core component of the WAVE complex, through its intracellular domain, suggesting a role in the control of actin assembly. Like that of Pcdh18b, depletion of Nap1 results in reduced branching of motor axons. Time-lapse imaging and quantitative analysis of axon dynamics indicate that both Pcdh18b and Nap1 regulate axon arborization by affecting the density of filopodia along the shaft of the extending axon.