Common mechanisms underlying growth cone guidance and axon branching
Common mechanisms underlying growth cone guidance and axon branching
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DOI：
10.1002/1097-4695(200008)44:2
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发表时间：
2000-08-01
期刊：
影响因子：
--
通讯作者：
Dent, EW
中科院分区：
文献类型：
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作者：
Kalil, K;Szebenyi, G;Dent, EW
在发育过程中，生长锥将咆哮的轴突引导到适当的目标。然而，在一些皮质通路中，靶神经支配通过从轴突轴延伸的侧支的发展而发生。这些分支是如何形成的？直接观察活体大脑皮层切片发现，在间质分支发育之前，胼胝体轴突的生长锥在其皮层靶点下方停留数小时。高分辨率成像分离的活皮层神经元数小时显示，生长锥划定的网站，未来轴突分支的长时间暂停行为和扩大的生长锥。在新的生长锥形成并恢复向前推进后，大的暂停生长锥的丝状伪足和板状伪足残留物留在轴突轴上，随后从轴突轴上出现间质分支。为了研究轴突分支点的细胞骨架重组，我们荧光标记了活的皮层神经元中的微管，并成像了微管在轴突轴和生长锥的新生长过程中的行为。在这两个区域中，微管通过张开和断裂重组成更具可塑性的形式。然后这些较短的微管以顺行和逆行运动侵入新发育的分支。虽然轴突分支的解离皮层神经元发生在没有目标，应用目标衍生的生长因子，FGF-2，大大增强分支。两者合计，这些结果表明，生长锥暂停是密切相关的轴突分支，并建议，共同的机制下定向轴突生长从终端生长锥和轴突轴。(C)John Wiley & Sons，Inc.
During development, growth cones direct growling axons into appropriate targets. However, in some cortical pathways target innervation occurs through the development of collateral branches that extend interstitially from the axon shaft. How do such branches form? Direct observations of living cortical brain slices revealed that growth cones of callosal axons pause for many hours beneath their cortical targets prior to the development of interstitial branches. High resolution imaging of dissociated living cortical neurons for many hours revealed that the growth cone demarcates sites of future axon branching by lengthy pausing behaviors and enlargement of the growth cone. After a new growth cone forms and resumes forward advance, filopodial and lamellipodial remnants of the large paused growth cone are left behind on the axon shaft from which interstitial branches later emerge. To investigate holy the cytoskeleton reorganizes at axon branch points, we fluorescently labeled microtubules in living cortical neurons and imaged the behaviors of microtubules during new grow th from the axon shaft and the growth cone. In both regions microtubules reorganize into a more plastic form by splaying apart and fragmenting. These shorter microtubules then invade newly developing branches with anterograde and retrograde movements. Although axon branching of dissociated cortical neurons occurs in the absence of targets, application of a target-derived growth factor, FGF-2, greatly enhances branching. Taken together, these results demonstrate that growth cone pausing is closely related to axon branching and suggest that common mechanisms underlie directed axon growth from the terminal growth cone and the axon shaft. (C) 2000 John Wiley & Sons, Inc.