Actin Reorganisation in Nerve Morphogenesis

Abstract

Anatomists over centuries have described nerve cells which are notable for their diversity of architectures ranging from rather simple cells to highly complex and beautiful shapes. The soma of most neurons has two types of projections – dendrites, which receive inputs from the environment or other nerve cells, and axons, which specialise in information transfer. The correct shape of a neuron and its connectivity which forms the basis of a functional circuit is crucial for the normal physiology of an animal. Defects in neuronal morphogenesis have been shown to be the cause of several neurological diseases. In this article, we focus on a key molecule – actin, a component of the cytoskeleton – that forms the basis of cell shape and growth. We discuss how signals from within the cells and from its developmental milieu influence the organisation of actin which in turn impacts on the shape and function of a nerve cell.

Key Concepts

  • Actin is enriched in areas of neurons which undergo rapid changes in shape.
  • Actin dynamics is regulated by multiple upstream signals and intracellular effectors.
  • Local destabilisation of the actin cytoskeleton is a key downstream event during selection of an axon.
  • Actin dynamics in the growth cone regulates filopodial extension/retraction.
  • Actin cytoskeleton is highly dynamic in dendritic spines.
  • Neuronal activity‐dependent spine enlargement is correlated with a shift in F‐/G‐actin equilibrium towards F‐actin.
  • Rho GTPases are major intracellular regulators of actin dynamics.

Keywords: actin; neuron; cytoskeleton; neuronal polarity; axon growth; dendritic patterning

Figure 1. Neuronal compartments in a Drosophila olfactory projection neuron. The dendrites receive input from the olfactory sensory neurons (not shown) within the antennal lobe. The axon projects to and synapses with higher centre in the brain. Image courtesy of Sonia Sen and Abhijit Das, NCBS.
Figure 2. Steps in nerve cell polarisation and neurite formation in culture: (a) Morphologically unpolarised neuron. (b) The neuron extends multiple equipotent neurites. (c) One neurite which grows rapidly becomes the axon, whereas the others become dendrites.
Figure 3. Organisation of actin and microtubule cytoskeleton in a growth cone: (a) Actin (in red) is enriched at the leading edge of the growth cone, whereas the central domain is rich in microtubules (blue). A few dynamic microtubules can be seen exploring the P‐domain (white arrow). (b) Schematic of a growth cone showing cytoskeletal organisation in the peripheral (P) and central (C) domains of a growth cone. The transition (T) zone is at the boundary between the P‐ and C‐domains. Image courtesy of Dylan Burnette Forscher Lab, Yale University.
Figure 4. (a) Dendritic arbour from a rodent brain decorated with spines. (b) Organisation of actin in a dendritic spine. Image courtesy of AK Shobha, Ruchi Malik and Sumantra Chattarji © NCBS Bangalore.
Figure 5. (a) Simple schematic showing molecular regulation of neuronal polarity in cultured neurons. Upstream signals regulate localisation of Rap1B in a single neurite which becomes the axon. Activation of Cdc42 and Par complex by Rap1B in turn leads to activation of Rac and cofilin leading to actin remodelling. Local destabilisation of actin facilitates invasion of distal areas of neurite by microtubules and subsequent specification of the neurite as an axon. (b) Pathways of regulation of actin dynamics leading to dendritic spine development, retraction and stabilisation. In the left panel, a pathway of neuronal activity‐dependent regulation is shown. The panel in the middle illustrates Eph signalling‐dependent regulation of spine formation through regulation of Cdc42 and Rac. The panel on the right illustrates the regulation of retraction by Eph signalling through Rho.
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Singh, Ajeet P, Rodrigues, Veronica, and VijayRaghavan, Krishnaswamy(Aug 2015) Actin Reorganisation in Nerve Morphogenesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021850.pub2]