Growth cones stall and collapse during axon outgrowth in Caenorhabditis elegans.
Growth cones stall and collapse during axon outgrowth in Caenorhabditis elegans.
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发表时间：
1999-10
期刊：
影响因子：
4.6
通讯作者：
Karla M. Knobel;Erik M. Jorgensen;M. Bastiani
中科院分区：
文献类型：
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作者：
Karla M. Knobel;Erik M. Jorgensen;M. Bastiani
在神经系统发育过程中，神经元与远处的靶细胞形成突触接触。这些联系是由轴突沿着预定的路径延伸形成的。轴突的生长是由位于这些神经元突起末端的生长锥体引导的。虽然生长锥在体外的行为已经很好地描述了，但在体内观察生长锥是困难的。我们用延时共聚焦显微镜观察了线虫幼虫体内运动神经元生长锥体的迁移。具体地说，我们观察到在L2阶段，VD运动神经元将轴突从腹侧延伸到背侧神经索。这些神经元的生长锥体是圆形的，如果畅通无阻，它们会迅速在表皮上迁移。当它们接触到外侧神经束的轴突时，生长锥体停止生长，并沿着神经束展开，形成砧状结构。在暂停几分钟后，它们将板脂延伸到神经束之外，并重新向背侧神经索迁移。当生长锥体接触到体壁肌肉时，它们会再次失速。这些肌肉通过狭窄间隔的环状附着结构紧密地附着在表皮上。停滞的生长锥在这些皮下附着结构之间向背侧伸展手指。当单个手指突出穿过体壁肌肉象限时，位于肌肉腹侧的生长锥体坍塌，在优势手指的背端形成新的生长锥体。因此，我们观察到完全的生长锥体塌陷发生在体内，而不仅仅是在培养试验中。与研究表明，VD生长锥的塌陷发生在与排斥底物接触时相反，VD生长锥的塌陷可能是一种内在信号的结果，该信号有助于维持生长锥的优势并保存细胞材料。
During nervous system development, neurons form synaptic contacts with distant target cells. These connections are formed by the extension of axonal processes along predetermined pathways. Axon outgrowth is directed by growth cones located at the tips of these neuronal processes. Although the behavior of growth cones has been well-characterized in vitro, it is difficult to observe growth cones in vivo. We have observed motor neuron growth cones migrating in living Caenorhabditis elegans larvae using time-lapse confocal microscopy. Specifically, we observed the VD motor neurons extend axons from the ventral to dorsal nerve cord during the L2 stage. The growth cones of these neurons are round and migrate rapidly across the epidermis if they are unobstructed. When they contact axons of the lateral nerve fascicles, growth cones stall and spread out along the fascicle to form anvil-shaped structures. After pausing for a few minutes, they extend lamellipodia beyond the fascicle and resume migration toward the dorsal nerve cord. Growth cones stall again when they contact the body wall muscles. These muscles are tightly attached to the epidermis by narrowly spaced circumferential attachment structures. Stalled growth cones extend fingers dorsally between these hypodermal attachment structures. When a single finger has projected through the body wall muscle quadrant, the growth cone located on the ventral side of the muscle collapses and a new growth cone forms at the dorsal tip of the predominating finger. Thus, we observe that complete growth cone collapse occurs in vivo and not just in culture assays. In contrast to studies indicating that collapse occurs upon contact with repulsive substrata, collapse of the VD growth cones may result from an intrinsic signal that serves to maintain growth cone primacy and conserve cellular material.