Abstract
Axons need to be properly guided to their targets to form synaptic connections, and this requires interactions between highly conserved extracellular and transmembrane ligands and their cell surface receptors. The majority of studies on axon guidance signaling pathways have focused on the role of these pathways in rearranging the local cytoskeleton and plasma membrane in growth cones and axons. However, a smaller body of work has demonstrated that axon guidance signaling pathways also control gene expression via local translation and transcription. Recent studies on axon guidance ligands and receptors have begun to uncover the requirements for these alternative mechanisms in processes required for neural circuit formation: axon guidance, synaptogenesis, and cell migration. Understanding the mechanisms by which axon guidance signaling regulates local translation and transcription will create a more complete picture of neural circuit formation, and they may be applied more broadly to other tissues where axon guidance ligands and receptors are required for morphogenesis. Developmental Dynamics 247:571-580, 2018. © 2017 Wiley Periodicals, Inc.
Highlights
The precise establishment of neural circuits during development is essential for coordinated animal behavior
The following axon guidance cues and receptors will be the focus of this review: 1) semaphorins and their neuropilin and plexin receptors, 2) Slits and their roundabout (Robo) receptors, 3) netrins and their deleted in colorectal carcinoma (Dcc), Frazzled (Fra, in Drosophila), Unc40, neogenin, and Unc5 receptors, and 4) ephrins and their Eph receptors (Hou et al, 2008)
Axon guidance pathways regulate axon guidance, synaptogenesis, progenitor dynamics, and cell migration using a variety of mechanisms
Summary
The precise establishment of neural circuits during development is essential for coordinated animal behavior. Most axon guidance receptors impinge on cytoplasmic proteins to regulate Rho family small GTPases, which in turn modulate cytoskeletal and membrane dynamics through diverse downstream effectors. Rho family GTPases can integrate signals from multiple cues to direct growth cone dynamics (Luo, 2002; O'Donnell et al, 2009). A smaller body of work has demonstrated that axon guidance cues and receptors act non-canonically to control cell proliferation, cell migration, and axon guidance by regulating gene expression through translational or transcriptional mechanisms. In this review we aim to synthesize the studies that investigate these mechanisms in an attempt to demonstrate that axon guidance ligands and receptors broadly function to regulate gene expression across a range of neuron subtypes, developmental processes, and organisms
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