Actin Reorganization in Nerve Morphogenesis

Ajeet Pratap Singh, TIFR, Mumbai, India
Veronica Rodrigues, TIFR, Mumbai, India
K VijayRaghavan, TIFR, Bangalore, India

Published online: March 2010

DOI: 10.1002/9780470015902.a0021850

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 have two types of projections – dendrites which receive inputs from the environment or other nerve cells, which specialize 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 organization 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 destabilization 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 polarization and neurite formation in culture: (a) Morphologically unpolarized neuron. (b) The neuron extends multiple equipotent neurites. (c) One neurite which grows rapidly becomes the axon, whereas the others become dendrites.
Figure 3. Organization 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). Image courtesy of Dylan Burnette and Paul Forscher, Yale University. (b) Schematic of a growth cone showing cytoskeletal organization 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.
Figure 4. (a) Dendritic arbor from a rodent brain decorated with spines. Image courtesy of AK Shobha, Ruchi Malik and Sumantra Chattarji, NCBS. (b) Organization of actin in a dendritic spine.
Figure 5. (a) Simple schematic showing molecular regulation of neuronal polarity in cultured neurons. Upstream signals regulate localization 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 destabilization 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 stabilization. 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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Related Sub-Topics:

Neurons | Intracellular and Extracellular Signalling | Cell Cytoskeleton | Cell Shape | Protein Structure
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Article Title: Actin Reorganization in Nerve Morphogenesis
 
How to Cite close
Singh, Ajeet Pratap, Rodrigues, Veronica, and VijayRaghavan, K(Mar 2010) Actin Reorganization in Nerve Morphogenesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021850]