Signalling mechanisms regulating axonal branching in vivo

Abstract

Identification of the molecular mechanisms underlying axonal branching in vivo has begun in several neuronal systems, notably the projections formed by dorsal root ganglion (DRG) neurons or retinal ganglion cells (RGC). cGMP signalling is essential for sensory axon bifurcation at the spinal cord, whereas brain-derived neurotrophic factor (BDNF) and ephrinA signalling establish position-dependent branching of RGC axons. In the latter system, the degradation of specific signalling components, via the ubiquitin-proteasome system, may provide an additional mechanism involved in axon branching of RGC. The process of arborisation is essential for neurons to innervate multiple targets and to build topographic maps. The various forms of branching found in different types of neurons are regulated by distinct signalling pathways activated by multiple extracellular cues in addition to axonal guidance factors. These signalling cascades, together with transcriptional programs, most likely interact and trigger the polymerisation or depolymerisation of the actin and tubulin cytoskeleton to regulate branching.

Developmental regulation of axon branching in the vertebrate nervous system

“…In the following sections we discuss how these steps are regulated by extracellular cues and by neural activity to generate stereotyped branches during development. The cellular mechanisms of their regulation (see Box 2) have been reviewed recently (Dent et al, 2003;Kornack and Giger, 2005;Schmidt and Rathjen, 2010) and will therefore only be discussed in the appropriate context.…”

“…We also highlight the critical steps that are shared among different branching processes during embryonic and postnatal development. We hope that, in combination with concomitant advances in our knowledge of the intracellular regulation of branching (for reviews, see Dent et al, 2003;Kornack and Giger, 2005;Schmidt and Rathjen, 2010), this review will bring us closer to understanding an important developmental process in the assembly of complex neural circuits in vertebrates. Box 1.…”

The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM–EGL-15/FGFR Receptor Complex

“…During development neurons often form branches to increase the possibilities for synaptic input and output (Schmidt and Rathjen, 2010; Gibson and Ma, 2011). Moreover, branching has been mechanistically linked to synapse formation (Chia et al, 2014) suggesting that it is an essential process during neural circuit assembly.…”

“…Moreover, branching has been mechanistically linked to synapse formation (Chia et al, 2014) suggesting that it is an essential process during neural circuit assembly. However, the molecular pathways that govern neuronal branching remain poorly understood and only a limited number of branching factors have been identified (Schmidt and Rathjen, 2010; Gibson and Ma, 2011). One of these, KAL-1/anosmin-1, encodes a putative secreted cell adhesion molecule, which when mutated causes Kallmann Syndrome (KS) in humans (Franco et al, 1991; Legouis et al, 1991).…”

The Pros and Cons of Growth Factors and Cytokines in Peripheral Axon Regeneration

“…During terminal branching, the bifurcation of the growth cone gives rise to two or more axon branches. In contrast, interstitial branching results in de novo initiation of axon branches from previously quiescent regions of the axon (Bastmeyer & O'Leary, 1996;Schmidt & Rathjen, 2010). Terminal branching is believed to occur only during early axonal outgrowth, whereas interstitial branching is observed during development and regeneration.…”