Szebenyi G, Callaway J L, Dent E W, Kalil K
Department of Anatomy, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Neurosci. 1998 Oct 1;18(19):7930-40. doi: 10.1523/JNEUROSCI.18-19-07930.1998.
Interstitial branches arise from the axon shaft, sometimes at great distances behind the primary growth cone. After a waiting period that can last for days after extension of the primary growth cone past the target, branches elongate toward their targets. Delayed interstitial branching is an important but little understood mechanism for target innervation in the developing CNS of vertebrates. One possible mechanism of collateral branch formation is that the axon shaft responds to target-derived signals independent of the primary growth cone. Another possibility is that the primary growth cone recognizes the target and demarcates specific regions of the axon for future branching. To address whether behaviors of the primary growth cone and development of interstitial branches are related, we performed high-resolution time-lapse imaging on dissociated sensorimotor cortical neurons that branch interstitially in vivo. Imaging of entire cortical neurons for periods of days revealed that the primary growth cone pauses in regions in which axon branches later develop. Pausing behaviors involve repeated cycles of collapse, retraction, and extension during which growth cones enlarge and reorganize. Remnants of reorganized growth cones are left behind on the axon shaft as active filopodial or lamellar protrusions, and axon branches subsequently emerge from these active regions of the axon shaft. In this study we propose a new model to account for target innervation in vivo by interstitial branching. Our model suggests that delayed interstitial branching results directly from target recognition by the primary growth cone.
间质分支起源于轴突干，有时在初级生长锥后方很远的位置。在初级生长锥延伸越过靶标后，会有一段可能持续数天的等待期，之后分支会朝着它们的靶标延伸。延迟的间质分支是脊椎动物发育中的中枢神经系统中靶标神经支配的一种重要但了解甚少的机制。侧支形成的一种可能机制是轴突干独立于初级生长锥对靶标衍生信号作出反应。另一种可能性是初级生长锥识别靶标并划定轴突的特定区域以便将来分支。为了研究初级生长锥的行为与间质分支的发育是否相关，我们对在体内进行间质分支的解离感觉运动皮层神经元进行了高分辨率延时成像。对整个皮层神经元进行数天的成像显示，初级生长锥会在轴突分支后来发育的区域暂停。暂停行为包括反复的塌陷、回缩和延伸循环，在此期间生长锥会扩大并重新组织。重新组织的生长锥的残余物作为活跃的丝状伪足或片状突起留在轴突干上，随后轴突分支从轴突干的这些活跃区域出现。在这项研究中，我们提出了一个新模型来解释体内通过间质分支进行的靶标神经支配。我们的模型表明，延迟的间质分支直接源于初级生长锥对靶标的识别。
