Regulation of the actin cytoskeleton in the neuronal growth cone

During the development of the nervous system, axons and dendrites are guided to their targets throughout the brain and body through the detection of diffusible and surface-bound guidance cues. The growth cone, a specialized structure found at the tips of axons and dendrites, detects and interprets these cues. Activation of downstream intracellular singling pathways leads to changes in the cytoskeleton of the growth cone that affect its motility. Although a number of the key players in this system have been identified, the means by which the growth cone is able to directly rearrange its cytoskeleton in response to guidance cues is not known. In the following experiments, I have examined the roles of several known actin- binding proteins in the remodeling of the growth cone cytoskeleton. The Arp2/3 protein complex binds to an existing actin filament and nucleates formation of a daughter branch. Arp2/3 activity generates a dense actin network in fibroblast cells that drives membrane protrusions. However, the role of this activity in neuronal growth cones has not been established. We have used an inhibitory strategy to explore the requirement for Arp2/3 in growth cone morphology and function. Arp2/3 is not required for growth cone morphology or the generation of protrusive structures; however, it may be required for proper motility in response to axon guidance cues. Activity the EnaNASP family of proteins promotes the formation of long, unbranched filaments in fibroblast systems. Ena/VASP has also been genetically linked to axon guidance pathways in Drosophila, C. elegans, and mice.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Strasser, Geraldine A

Advisor dc:contributor.advisor

• Frank Gertler.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/31182
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/31182

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/31182