The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neurons, combined with genetic analysis and electron tomography, we have identified the Actin-related protein (Arp) 2/3 complex as the major actin nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks the site of branchlet initiation in vivo. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation.

Highlights d Elevated actin turnover is essential for regenerative growth d ADF/cofilin activity increases during conditioning-mediated regeneration d ADF/cofilin is necessary and sufficient for axon regeneration d The severing activity of ADF/cofilin is critical for axon regeneration

Highlights d CNS neurons polarize and grow their axon in 3D similarly to in situ d The axon grows in 3D unrestrained of actin filaments d The axon extends without pulling on the extracellular matrix d The growth cone does not need adhesion sites for axon extension in 3D

Highlights d Axon growth-competent adult neurons downregulate critical components of the synapse d Pharmacogenetic reduction of neuronal excitability stimulates axon regeneration d The presynaptic active zone proteins Munc13 and RIM suppress axon growth d Systemic Baclofen treatment promotes regeneration after adult spinal cord injury Authors

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