Branch management: mechanisms of axon branching in the developing vertebrate CNS

Abstract

The remarkable ability of a single axon to extend multiple branches and form terminal arbors allows vertebrate neurons to integrate information from divergent regions of the nervous system. Axons select appropriate pathways during development, but it is the branches that extend interstitially from the axon shaft and arborize at specific targets that are responsible for virtually all of the synaptic connectivity in the vertebrate CNS. How do axons form branches at specific target regions? Recent studies have identified molecular cues that activate intracellular signalling pathways in axons and mediate dynamic reorganization of the cytoskeleton to promote the formation of axon branches.

Kinesin-1 sorting in axons controls the differential retraction of arbor terminals

“…To connect with multiple target cells, neurons elaborate the axonal arbor by controlling growth and retraction during development (Gibson and Ma, 2011;Kalil and Dent, 2014). Previous in vivo (Portera-Cailliau et al, 2005;Hua et al, 2005;Meyer and Smith, 2006;Stettler et al, 2006;Nishiyama et al, 2007) and in vitro (Bastmeyer and O'Leary, 1996;Ruthel and Hollenbeck, 2000) studies have revealed the diverse plasticity of arbor terminals in a single axon.…”

Mechanisms of Differential Branch Growth Control in the Single Axonal Arbor

“…Neurons extend one long axonal process for transmitting signals to distantly located postsynaptic targets. During nervous system development, neurons form axonal branches, sending signals to multiple targets, with some branches simultaneously eliminated by retraction [1][2][3]. This process, called axonal remodeling, is crucial for generating proper neuronal wiring.…”

“…In collateral branch formation, a major mode of axonal branching, an F-actin patch is initially formed at the branch site and serves as a precursor for a filopodium or lamellipodium. After the emergence of these F-actin-containing protrusions, microtubules innervate the branch [2,8]. These processes have been extensively studied using young axons of sensory neurons.…”

Building branched tissue structures: from single cell guidance to coordinated construction

“…In general, as the mechanisms of branching include a greater number of cells that contribute to branch formation, the regulation of collective movements of cellular cohorts increases. For example, axon branching within the neuronal network requires the morphogenetic action of a single cell responding to guidance cues [1]. This action guides axons to appropriately innervate multiple target tissues (figure 1).…”