Initiating and Growing an Axon

Abstract

The ability of neurons to form a single axon and multiple dendrites underlies the directional flow of information transfer in the central nervous system. Dendrites and axons are molecularly and functionally distinct domains. Dendrites integrate synaptic inputs, triggering the generation of action potentials at the level of the soma. Action potentials then propagate along the axon, which makes presynaptic contacts onto target cells. This article reviews what is known about the cellular and molecular mechanisms underlying the ability of neurons to initiate and extend a single axon during development. Remarkably, neurons can polarize to form a single axon, multiple dendrites, and later establish functional synaptic contacts in reductionist in vitro conditions. This approach became, and remains, the dominant model to study axon initiation and growth and has yielded the identification of many molecules that regulate axon formation in vitro (Dotti et al. 1988). At present, only a few of the genes identified using in vitro approaches have been shown to be required for axon initiation and outgrowth in vivo. In vitro, axon initiation and elongation are largely intrinsic properties of neurons that are established in the absence of relevant extracellular cues. However, the importance of extracellular cues to axon initiation and outgrowth in vivo is emerging as a major theme in neural development (Barnes and Polleux 2009). In this article, we focus our attention on the extracellular cues and signaling pathways required in vivo for axon initiation and axon extension.

Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro

“…Several initial candidates for downstream targets failed our tests of involvement. Although contact mediated cues are important for axon outgrowth and branching (for review, see Polleux and Snider, 2010;Raper and Mason, 2010), we found no evidence for structural alterations in the AIS, branching pattern, axonal length, or cholesterol content that can readily explain the strong propagation changes. Furthermore, although axon-specific potassium channels are prime candidates to explain the severe disruption of axonal signal propagation, we found no evidence for alterations in a putative axon-specific, principal-neuron potassium channel, K v 7.2/3.…”

LMTK1/AATYK1 Is a Novel Regulator of Axonal Outgrowth That Acts via Rab11 in a Cdk5-Dependent Manner

“…Axonal outgrowth is a coordinated process of cytoskeletal reorganization and membrane transport (Tang, 2001;Arimura and Kaibuchi, 2007;Polleux and Snider, 2010). This process has been extensively investigated, and a number of molecules involved in neurite outgrowth have been delineated in recent years.…”

“…Neither axon formation nor polarity was affected by knockdown or knockout of LMTK1. Several molecules with axonal outgrowth activity determine polarity rather than regulate axon length itself (Polleux and Snider, 2010), but LMTK1 is not a polarity-establishing protein. Because total neurite length did not change after the overexpression of LMTK1-S34A or the knockdown of LMTK1, axons were lengthened at the expense of the elongation of other neurites.…”

“…Axonal elongation includes the coordinated actions of cytoskeletal rearrangements and directed membrane delivery. Although the cytoskeletal components involved in axonal elongation have been studied extensively (Arimura and Kaibuchi, 2007;Polleux and Snider, 2010), little is known about the molecular mechanism of membrane supply to the axons (Sann et al, 2009;Bloom and Morgan, 2011).…”

The cellular and molecular mechanisms of axonal maintenance and regeneration

“…The establishment of these two neuronal compartments is essential for correct neuronal function, and occurs soon after the neuron is born. Growing evidence, primarily from in vitro studies, suggests that regulation of the microtubule cytoskeleton provides key instructive signals to specify axon and dendrite identity (Polleux and Snider, 2010). In addition to their role in neuronal polarity during development, microtubule dynamics have been recently implicated in axonal regeneration and degeneration (reviewed in chapter 1).…”