Growth Cone Travel in Space and Time: the Cellular Ensemble of Cytoskeleton, Adhesion, and Membrane

Abstract

Growth cones, found at the tip of axonal projections, are the sensory and motile organelles of developing neurons that enable axon pathfinding and target recognition for precise wiring of neural circuitry. To date, many families of conserved guidance molecules and their corresponding receptors have been identified that work in space and time to ensure billions of axons to their targets. Research in the past two decades has also gained significant insight into the mechanisms by which growth cones translate extracellular signals into directional migration. This review aims to examine new progress towards understanding the cellular mechanisms underlying directional motility of the growth cone and to discuss questions that remain to be addressed. Specifically we will focus on the cellular ensemble of cytoskeleton, adhesion, and membrane and examine how the intricate interplay between these processes orchestrates the directed movement of growth cones.

Interaction of leech neurons with topographical gratings: comparison with rodent and human neuronal lines and primary cells

“…Extracellular nano/microtopography signals are locally retrieved through a complex phenomenon called contact guidance and can drive many neuronal activities, such as differentiation, polarization, neurite pathfinding, nucleokinesis and the final CNS wiring [10][11][12][13][14][15][16]. These processes are tightly regulated and involve coordinated interactions between microtubules and the actin cytoskeleton [16,17] as well as the establishment and maturation of focal adhesions (FAs) [18].…”

Collapsin Response Mediator Protein 4 Regulates Growth Cone Dynamics through the Actin and Microtubule Cytoskeleton

“…Rearrangements of the actin cytoskeletal network at the growth cone leading edge, exploratory extension of microtubules into the peripheral domain, and protrusion of stabilizing microtubules behind extending lamellipodia and filopodia are all critical for directed outgrowth (1). Overlap between the actin and microtubule networks in the transition domain of the growth cone plays a key role in generating force required for neurite extension (2).…”

Regulating small G protein signaling to coordinate axon adhesion and repulsion

“…The growth cone is a highly motile structure comprised of spike-like filopodia and web-like lamellipodia. 3,4 Filopodia are supported in part by bundled, parallel-organized filamentous actin, while lamellipodia are comprised of a mesh-like network of actin. In addition to these actin structures, microtubules strengthen the long axon shaft and also…”

“…1 A simplified view of this movement is that initial cellular protrusions such as filopodia and lamellipodia develop by actin nucleation/polymerization. [2][3][4] These protrusions are stabilized by attaching to the extracellular matrix (ECM) or adjacent cells, which are connected to the actin cytoskeleton and provide "feet" for migration. [4][5][6] These steps cycle in the course of motility.…”