Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208.
Laboratory of Organogenesis and Organ Function, Bioscience and Biotechnology Center, Nagoya University, Nagoya 464-8601, Aichi, Japan.
eNeuro. 2019 Sep 18;6(5). doi: 10.1523/ENEURO.0026-19.2019. Print 2019 Sep/Oct.
Mitochondria are abundantly detected at the growth cone, the dynamic distal tip of developing axons that directs growth and guidance. It is, however, poorly understood how mitochondrial dynamics relate to growth cone behavior , and which mechanisms are responsible for anchoring mitochondria at the growth cone during axon pathfinding. Here, we show that in retinal axons elongating along the optic tract in zebrafish, mitochondria accumulate in the central area of the growth cone and are occasionally observed in filopodia extending from the growth cone periphery. Mitochondrial behavior at the growth cone is dynamic, with mitochondrial positioning and anterograde transport strongly correlating with growth cone behavior and axon outgrowth. Using novel zebrafish mutant lines that lack the mitochondrial anchoring proteins Syntaphilin a and b, we further show that Syntaphilins contribute to mitochondrial immobilization at the growth cone. Syntaphilins are, however, not required for proper growth cone morphology and axon growth , indicating that Syntaphilin-mediated anchoring of mitochondria at the growth cone plays only a minor role in elongating axons.
线粒体在生长锥中大量存在，生长锥是发育中的轴突的动态远端尖端，指导生长和导向。然而，人们对线粒体动力学与生长锥行为的关系以及哪些机制负责在轴突寻径过程中将线粒体锚定在生长锥上知之甚少。在这里，我们发现在沿着斑马鱼视束伸长的视网膜轴突中，线粒体积累在生长锥的中央区域，并且偶尔在从生长锥外围延伸的丝状伪足中观察到线粒体。生长锥处的线粒体行为是动态的，线粒体的定位和正向运输与生长锥行为和轴突生长强烈相关。使用缺乏线粒体锚定蛋白 Syntaphilin a 和 b 的新型斑马鱼突变系，我们进一步表明 Syntaphilins 有助于线粒体在生长锥处的固定。然而，Syntaphilins 对于生长锥的形态和轴突生长不是必需的，这表明 Syntaphilin 介导的线粒体在生长锥处的锚定在伸长轴突中仅起次要作用。
