Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system.
Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system.
复制标题
Frazzled促进果蝇视觉系统中Netrin梯度来源的生长锥附着。
DOI：
10.7554/elife.20762
复制
发表时间：
2016-10-15
期刊：
影响因子：
7.7
通讯作者：
Zipursky SL
中科院分区：
文献类型：
--
作者：
Akin O;Zipursky SL
轴突引导被认为是通过长程和短程吸引和排斥信号的组合来起作用的。配体受体对Netrin （Net）和frazzed (Fra) （DCC，在结直肠癌中缺失，在脊椎动物中）被认为是化学吸引的典型效应体，在远程和短程引导中都有作用。在果蝇的视觉系统中，R8光感受器生长锥需要Net- fra才能到达它们的目标，即Net梯度的峰值。然而，通过实时成像，我们发现R8生长锥在没有Net、Fra或Trim9 （Fra的保守结合伙伴）的情况下到达并识别它们的目标，但不保持附着。因此，尽管配体沿引导路径呈梯度分布，Net-Fra不用于化学吸引。基于其他系统的研究结果，我们提出，对基质结合的净的粘附是体内依赖净-氟的长距离和短程引导的基础，从而削弱了它们之间的区别。DOI: http://dx.doi.org/10.7554/eLife.20762.001果蝇的大脑包含数十万个神经元，而人类的大脑包含超过800亿个神经元。每一个都由一个细胞体组成，细胞体上有一系列被称为树突的分支，外加一个单根索状的轴突。在发育过程中，神经元通过轴突和树突相互连接，形成复杂的网络。但目前尚不清楚正确的连接是如何在正确的位置形成的。随着轴突的生长，它们依靠尖端的特殊运动结构——生长锥——探测周围的环境，寻找其他细胞释放的吸引和排斥的化学信号。当生长锥表面的传感器检测到目标信号时，它们启动导致生长锥扩张或收缩的过程。这使得轴突可以根据需要向信号方向移动或远离信号。在所有被研究的动物中，被称为DCC和Netrin的蛋白质形成了最著名的传感器信号对之一。承载DCC传感器的生长锥被认为可以探测到“飘浮的羽状物”或Netrin的梯度，然后向Netrin源方向生长。然而，没有人直接观察过活的完整动物的神经元对Netrin的反应。使用一种可以深入观察苍蝇大脑发育的显微镜，Akin和Zipursky现在已经跟踪了果蝇蛹中R8神经元细胞上生长锥的运动。出乎意料的是，Akin和Zipursky发现，缺乏Netrin或frazzed（果蝇版本的DCC）的突变果蝇的生长锥成功地导航到它们预定的目的地。然而，一旦到达那里，突变的生长锥就无法附着在它们的目标上。Akin和Zipursky的工作与其他一些动物和昆虫系统的观察结果一致，这些观察表明Netrin可能不是通过飘动的信号羽状物来吸引生长锥的。相反，Netrin可能会形成一个粘性的轨迹，帮助生长锥在向目的地爬行或粘在目的地时获得牵引力。现在需要进一步的实验来测试果蝇和其他动物的其他神经元是否以这种方式使用Netrin。DOI: http://dx.doi.org/10.7554/eLife.20762.002
Axon guidance is proposed to act through a combination of long- and short-range attractive and repulsive cues. The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both long- and short-range guidance. In the Drosophila visual system, R8 photoreceptor growth cones were shown to require Net-Fra to reach their target, the peak of a Net gradient. Using live imaging, we show, however, that R8 growth cones reach and recognize their target without Net, Fra, or Trim9, a conserved binding partner of Fra, but do not remain attached to it. Thus, despite the graded ligand distribution along the guidance path, Net-Fra is not used for chemoattraction. Based on findings in other systems, we propose that adhesion to substrate-bound Net underlies both long- and short-range Net-Fra-dependent guidance in vivo, thereby eroding the distinction between them. DOI: http://dx.doi.org/10.7554/eLife.20762.001 The brain of the fruit fly contains hundreds of thousands of neurons, while the human brain contains more than 80 billion. Each of these consists of a cell body that bears an array of branches called dendrites, plus a single cable-like axon. During development, the neurons organize themselves into complex networks by forming connections with one another via their axons and dendrites. But it is not clear exactly how the correct connections form in the correct places. As they grow out, axons rely on specialized moving structures at their tips – known as growth cones – to probe their environment in search of attractive and repulsive chemical signals released by other cells. When sensors on the surface of growth cones detect a target signal, they initiate processes that cause the growth cone to expand or collapse. This enables the axons to move towards or away from the signal, as appropriate. In all animals studied, proteins called DCC and Netrin form one of the best-known sensor-signal pairs. Growth cones bearing DCC sensors are thought to detect ‘wafting plumes’ or gradients of Netrin and then grow towards the Netrin source. However, nobody had directly watched neurons respond to Netrin in a living intact animal. Using a type of microscope that can look deep into the developing fly brain, Akin and Zipursky have now followed the movement of growth cones on cells called R8 neurons in fruit fly pupae. Unexpectedly, Akin and Zipursky found that the growth cones of mutant flies that lack Netrin or Frazzled (the fruit fly version of DCC) navigate successfully to their intended destinations. Once there, however, the mutant growth cones were unable to attach to their targets. Akin and Zipursky’s work is consistent with other observations in a number of animal and insect systems that suggest that Netrin may not attract growth cones via wafting plumes of signal. Instead, Netrin may form a sticky trail that helps growth cones to gain traction as they crawl towards or stick to their destinations. Further experiments are now needed to test whether other neurons in fruit flies and in different animals use Netrin in this way. DOI: http://dx.doi.org/10.7554/eLife.20762.002