Department of Organismal Biology and Anatomy, The University of Chicago, Chicago, IL 60637, USA.
Development. 2013 Feb;140(4):906-15. doi: 10.1242/dev.087148. Epub 2013 Jan 16.
Appropriate localization of neurons within the brain is a crucial component of the establishment of neural circuitry. In the zebrafish hindbrain, the facial branchiomotor neurons (FBMNs) undergo a chain-like tangential migration from their birthplace in rhombomere (r) 4 to their final destination in r6/r7. Here, we report that ablation of either the cell body or the trailing axon of the leading FBMN, or 'pioneer' neuron, blocks the migration of follower FBMNs into r5. This demonstrates that the pioneer neuron and its axon are crucial to the early migration of FBMNs. Later migration from r5 to r6 is not dependent on pioneer neurons but on the medial longitudinal fasciculus (MLF), a bundle of axons lying ventral to the FBMNs. We find that MLF axons enter r5 only after the pioneer neuron has led several followers into this region; the MLF is then contacted by projections from the FBMNs. The interactions between FBMNs and the MLF are important for migration from r5 to r6, as blocking MLF axons from entering the hindbrain can stall FBMN migration in r5. Finally, we have found that the adhesion molecule Cdh2 (N-cadherin) is important for interactions between the MLF and FBMNs, as well as for interactions between the trailing axon of the pioneer neuron and follower FBMNs. Interestingly, migration of pioneer neurons is independent of both the MLF and Cdh2, suggesting pioneer migration relies on independent cues.
神经元在大脑中的适当定位是建立神经回路的关键组成部分。在斑马鱼后脑中，面神经运动神经元（FBMNs）从它们在栉状 4 区的发源地进行链状切线迁移，到达最终目的地栉状 6/7 区。在这里，我们报告说，领先 FBMN 的细胞体或尾随轴突的消融，或“先驱”神经元，会阻止后续 FBMN 迁移到 r5。这表明先驱神经元及其轴突对于 FBMN 的早期迁移至关重要。从 r5 到 r6 的后期迁移不依赖于先驱神经元，而是依赖于位于 FBMN 腹侧的中纵束（MLF），这是一束轴突。我们发现 MLF 轴突仅在先驱神经元将几个追随者引导到该区域后才进入 r5；然后，来自 FBMN 的投射与 MLF 接触。FBMN 和 MLF 之间的相互作用对于从 r5 到 r6 的迁移很重要，因为阻止 MLF 轴突进入后脑可以使 FBMN 在 r5 中的迁移停滞。最后，我们发现黏附分子 Cdh2（N-钙黏蛋白）对于 MLF 和 FBMN 之间的相互作用以及先驱神经元的尾随轴突和后续 FBMN 之间的相互作用很重要。有趣的是，先驱神经元的迁移独立于 MLF 和 Cdh2，这表明先驱迁移依赖于独立的线索。
