REGULATION OF NEURONAL POLARITY BY CHANGING ACTIN AND MICROTUBULE DYNAMICS

Open Access
- Author:
- Qin, Mengying
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Sarah Mary Assmann, Thesis Supervisor
Dr. Gong Chen, Thesis Supervisor
Sarah Mary Assmann, Thesis Honors Advisor - Keywords:
- Cofilin
Neuronal Polarity
Actin - Abstract:
- Neurons are remarkable in that their polarized morphology is essential for its function of unidirectional information passage. The polarity of a neuronal cell is marked by the presence of a single axon and multiple dendrites. Here, we report that cofilin and its upstream regulators LIM kinase (LIMK) and Slingshot (SSH) are critical for axonal formation. We studied the role of cofilin in axonal regulation by disrupting cofilin and its regulators during critical time periods of neuritogenesis and axogenesis in cortical neuron cultures. We found that loss of cofilin, LIMK or SSH greatly reduced the percentage of single axon neurons. Contrarily, overexpression of cofilin or LIMK did not affect axonal determination but the overexpression of SSH prevented the formation of axons in many cells. As cytoskeleton activity is known to be crucial to axon formation, we co-expressed cofilin shRNA with the cytoskeleton proteins actin and tubulin in an attempt to repair the deleterious effects of cofilin knockdown. It appears that actin overexpression alone induced multiple axons, and also rescued axon defects caused by cofilin shRNA. Similar phenomena were observed when actin was co-expressed with LIMK shRNA as well as with SSH shRNA. We found that defects from cofilin knockdown were highly correlated to the actin activity and less dependent on tubulin expression. Our results suggest that increased actin dynamics result in more axons, while decreased actin dynamics result in increased probability of no axons.