Ena/VASP function in retinal axons is required for terminal arborization but not pathway navigation.
Ena/VASP function in retinal axons is required for terminal arborization but not pathway navigation.
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DOI：
10.1242/dev.002345
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发表时间：
2007-06
期刊：
影响因子：
--
通讯作者：
Lebrand C
中科院分区：
文献类型：
--
作者：
Dwivedy A;Gertler FB;Miller J;Holt CE;Lebrand C
Enable/Vasp(Enable/Vasp)蛋白家族是生长锥体中丝状足形成所必需的，在引导线索诱导的肌动蛋白细胞骨架重塑中起着关键作用。对肌动蛋白聚合的药理抑制剂的体内研究先前已经提供了证据，证明在发育中的视觉通路中，生长锥导航需要丝状伪足。在这里，我们使用另一种策略重新研究了这个问题，该策略通过人工将Xena/XVASP(Xenopus Homologs of Ena/Vasp)蛋白定位于视网膜神经节细胞(RGC)的线粒体，从而在体内生成没有丝状足孔的生长锥体。我们利用Ena/Vasp蛋白家族的EVH1结构域与配体基序FP4的特异性结合来将蛋白质隔离在线粒体表面。Xena/XVASP蛋白功能降低的视网膜节细胞从眼外伸出的轴突较少，并有动态的板脂生长锥体，缺少在视束中缓慢推进的丝状足基。令人惊讶的是，尽管没有丝状足突，轴突仍然沿着视路导航，没有明显的引导错误，这表明Xena/XVASP蛋白家族和丝足突起对视网膜轴突的寻径不是必需的。然而，Xena/XVASP蛋白的缺失严重损害了生长锥在视顶盖内形成分支的能力，这表明该蛋白家族，可能还有丝状伪足，在建立末端分支中发挥了关键作用。
The Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family of proteins is required for filopodia formation in growth cones and plays a crucial role in guidance cue-induced remodeling of the actin cytoskeleton. In vivo studies with pharmacological inhibitors of actin polymerization have previously provided evidence for the view that filopodia are needed for growth cone navigation in the developing visual pathway. Here we have re-examined this issue using an alternative strategy to generate growth cones without filopodia in vivo by artificially targeting Xena/XVASP (Xenopus homologs of Ena/VASP) proteins to mitochondria in retinal ganglion cells (RGCs). We used the specific binding of the EVH1 domain of the Ena/VASP family of proteins with the ligand motif FP4 to sequester the protein at the mitochondria surface. RGCs with reduced function of Xena/XVASP proteins extended fewer axons out of the eye and possessed dynamic lamellipodial growth cones missing filopodia that advanced slowly in the optic tract. Surprisingly, despite lacking filopodia, the axons navigated along the optic pathway without obvious guidance errors, indicating that the Xena/XVASP family of proteins and filopodial protrusions are non-essential for pathfinding in retinal axons. However, depletion of Xena/XVASP proteins severely impaired the ability of growth cones to form branches within the optic tectum, suggesting that this protein family, and probably filopodia, plays a key role in establishing terminal arborizations.
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