Drebrin coordinates the actin and microtubule cytoskeleton during the initiation of axon collateral branches.

Drebrin is a cytoskeleton-associated protein which can interact with both actin filaments and the tips of microtubules. Its roles have been studied mostly in dendrites, and the functions of drebrin in axons are less well understood. In this study, we analyzed the role of drebrin, through shRNA-mediated depletion and overexpression, in the collateral branching of chicken embryonic sensory axons.

Nerve growth factor promotes reorganization of the axonal microtubule array at sites of axon collateral branching.

The localized debundling of the axonal microtubule array and the entry of microtubules into axonal filopodia are two defining features of collateral branching. We report that nerve growth factor (NGF), a branch-inducing signal, increases the frequency of microtubule debundling along the axon shaft of chicken embryonic sensory neurons. Sites of debundling correlate strongly with the localized targeting of microtubules into filopodia.

Involvement of Rho-family GTPases in axon branching.

Development of the nervous system requires efficient extension and guidance of axons and dendrites culminating in synapse formation. Axonal growth and navigation during embryogenesis are controlled by extracellular cues. Many of the same extracellular signals also regulate axonal branching.

Mitochondria coordinate sites of axon branching through localized intra-axonal protein synthesis.

The branching of axons is a fundamental aspect of nervous system development and neuroplasticity. We report that branching of sensory axons in the presence of nerve growth factor (NGF) occurs at sites populated by stalled mitochondria. Translational machinery targets to presumptive branching sites, followed by recruitment of mitochondria to these sites.

Axonally synthesized β-actin and GAP-43 proteins support distinct modes of axonal growth.

Increasing evidence points to the importance of local protein synthesis for axonal growth and responses to axotomy, yet there is little insight into the functions of individual locally synthesized proteins. We recently showed that expression of a reporter mRNA with the axonally localizing β-actin mRNA 3'UTR competes with endogenous β-actin and GAP-43 mRNAs for binding to ZBP1 and axonal localization in adult sensory neurons (Donnelly et al., 2011).

Nerve growth factor-induced formation of axonal filopodia and collateral branches involves the intra-axonal synthesis of regulators of the actin-nucleating Arp2/3 complex.

Nerve growth factor (NGF) induces collateral branching along sensory axons by promoting the formation of axonal filopodia dependent on the actin-nucleating Arp2/3 complex. This study shows that chicken embryonic sensory axons contain mRNAs for the actin-nucleating Arp2/3 complex activator WAVE1 and the complex stabilizer cortactin. NGF increases the axonal levels of WAVE1 and cortactin through localized protein synthesis even in axons isolated from the cell body.

The actin nucleating Arp2/3 complex contributes to the formation of axonal filopodia and branches through the regulation of actin patch precursors to filopodia.

The emergence of axonal filopodia is the first step in the formation of axon collateral branches. In vitro, axonal filopodia emerge from precursor cytoskeletal structures termed actin patches. However, nothing is known about the cytoskeletal dynamics of the axon leading to the formation of filopodia in the relevant tissue environment.

Mechanism of NGF-induced formation of axonal filopodia: NGF turns up the volume, but the song remains the same?

The formation of axon collateral branches is a fundamental aspect of the development of neuronal circuits. Emergence of axonal filopodia from the axon is the first step in the formation of axon collateral branches and pre-synaptic structures. Using embryonic sensory axons as a model system, we have determined that axonal filopodia are formed from transient accumulations of F-actin within the axon, termed actin patches.