Nervous system development proceeds via well‐orchestrated processes involving a balance between progressive and regressive events including stabilization or elimination of axons, synapses, and even entire neurons. These progressive and regressive events are driven by functionally antagonistic signaling pathways with the dominant pathway eventually determining whether a neural element is retained or removed. Many of these developmental sculpting events are triggered by final target innervation necessitating a long‐distance mode of communication. While long‐distance progressive signaling has been well characterized, particularly for neurotrophic factors, there remains relatively little known about how regressive events are triggered from a distance. Here we discuss the emergent phenomenon of long‐distance regressive signaling pathways. In particular, we will cover (a) progressive and regressive cues known to be employed after target innervation, (b) the mechanisms of long‐distance signaling from an endosomal platform, (c) recent evidence that long‐distance regressive cues emanate from platforms like death receptors or repulsive axon guidance receptors, and (d) evidence that these pathways are exploited in pathological scenarios.

中文翻译：

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神经发育和疾病中的长距离回归信号

神经系统的发育通过精心策划的过程进行，涉及渐进和退化事件之间的平衡，包括轴突、突触甚至整个神经元的稳定或消除。这些渐进和退步事件由功能拮抗信号通路驱动，主导通路最终决定神经元件是保留还是移除。许多这些发育性雕刻事件是由最终目标神经支配触发的，因此需要长距离通信模式。虽然长距离渐进信号已被很好地表征，特别是对于神经营养因子，但关于如何从远处触发回归事件仍然知之甚少。在这里，我们讨论长距离回归信号通路的新兴现象。特别是，