Abstract
The development of neural circuits is a complex process that relies on the proper navigation of axons through their environment to their appropriate targets. While axon–environment and axon–target interactions have long been known as essential for circuit formation, communication between axons themselves has only more recently emerged as another crucial mechanism. Trans-axonal signaling governs many axonal behaviors, including fasciculation for proper guidance to targets, defasciculation for pathfinding at important choice points, repulsion along and within tracts for pre-target sorting and target selection, repulsion at the target for precise synaptic connectivity, and potentially selective degeneration for circuit refinement. This review outlines the recent advances in identifying the molecular mechanisms of trans-axonal signaling and discusses the role of axon–axon interactions during the different steps of neural circuit formation.
Highlights
The formation of neural circuits is a complex developmental process that gives rise to intricate and precise networks essential for brain function [1,2]
We describe specific examples that highlight the importance of trans-axonal signaling in circuit wiring during development, focusing on the mechanisms underlying selective fasciculation and adhesion, repulsion, and selective defasciculation
Trans-axonal signaling regulates a striking number of developmental processes that are essential for neural circuit wiring
Summary
The formation of neural circuits is a complex developmental process that gives rise to intricate and precise networks essential for brain function [1,2]. A panoply of factors are known to provide long-range and/or contact-mediated signals, including the classical guidance cues Ephrins, Slits, Netrins, and Semaphorins [13], adhesion molecules [14,15], neurotrophic and growth factors [16], or morphogens such as Sonic Hedgehog (Shh), Bone morphogenetic proteins (BMPs), and Wnts [17,18] The activity of these signaling factors has mostly been studied in classical model systems for axon guidance such as the sensory and motor innervation of the limb [19], the midline [20,21], and the retinotectal and olfactory systems [22,23,24,25]. We describe specific examples that highlight the importance of trans-axonal signaling in circuit wiring during development, focusing on the mechanisms underlying selective fasciculation and adhesion, repulsion, and selective defasciculation
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