Dissertation
Functional consequences of developmental changes in the actomyosin and microtubule cytoskeleton in axonal morphogenesis
Doctor of Philosophy (Ph.D.), Drexel University
Apr 2011
DOI:
https://doi.org/10.17918/00008307
Abstract
Formation of the nervous system requires the establishment of functional connections between individual neurons and specific target tissue. During early embryonic development neurons extend axons from their cell bodies that are directed to their targets by a specialized structure at the tip of the axon termed the growth cone. The growth cone is highly dynamic and directs axon extension by responding to guidance cues in the extracellular environment of the developing embryo. The growth cone is dependent on the dynamics and organization of the actin filament (F-actin) and microtubule (MT) cytoskeleton. In the older postnatal or adult nervous system, the ability of axons to undergo directed axon extension is required for the re-establishment of functional connectivity after injury. Failure of axons to regenerate is due in part to an inhibitory extracellular environment. However, mounting evidence suggests that the diminished capacity to regenerate is also partly due to changes that occur within neurons during development. In this thesis I show that both the F-actin and MT cytoskeleton undergo developmental changes in the organization and levels of cytoskeletal proteins between embryonic day (E) 7 and E14 in chick dorsal root ganglion (DRG) neurons and that these changes have functional consequences on the mechanism of axon extension. Although both F-actin and MTs contribute to axon extension at both E7 and E14, the mechanism of axon extension changes from a mechanism strictly dependent on F-actin and partly dependent on MTs at E7 to one more dependent on MT dynamics and less on F-actin by E14. Furthermore, the levels of the F-actin motor protein myosin II undergo a developmental down-regulation between E7 and E14. The down-regulation of myosin II levels is accompanied by a decrease in the requirement for myosin II in axon extension, and contributes to a transition from an extension mode of axon development to an arborization/branching mode. Collectively, these observations demonstrate that developmental changes in the neuronal cytoskeleton have consequences on the mechanisms of axon extension.
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Details
- Title
- Functional consequences of developmental changes in the actomyosin and microtubule cytoskeleton in axonal morphogenesis
- Creators
- Steven L. Jones
- Contributors
- Gianluca Gallo (Advisor) - Drexel University, Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiv, 177 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Other Identifier
- 991021888894004721