Abstract
Axonal growth is a fundamental process in nerve development and regeneration. This process is regulated by the growth cone, the sensory motile tip of the growing axon. Growth cone shape and motility have been examined under a wide variety of conditions related to developmental and regeneration environments, but we still lack a basic framework for understanding key mechanisms determining growth cone motility and axonal growth. The cytoskeletal proteins, actin and tubulin, are thought to play important roles. Previous work by our group has focused on microtubule contribution to growth cone motility. To address the contribution of the cytoskeletal actin, a model was developed to describe actin dynamics within the growth cone. Actin polymerization at the leading front of the growth cone was assumed to be responsible for protrusion while a constant retrograde force acting throughout the growth cone yielded a rearward flow of polymer. The balance between polymerization and retrograde flow was reflected in the resulting growth cone motility. In addition, the growth cone was assumed to be attached to its growth substrate through receptor-mediated interactions at the leading front. This was represented in the model by a substrate attachment factor. Model parameters were estimated from both experimental measurements and literature values. The model was used to simulate growth cone movement on a uniform substrate, and shape characteristics of the simulated growth cone were compared to experimental growth cones in vitro. These results show that the model is consistent with current observations and suggest further experiments needed to develop and validate the model.
| Original language | American English |
|---|---|
| Pages (from-to) | A756 |
| Journal | FASEB Journal |
| Volume | 12 |
| Issue number | 5 |
| State | Published - Mar 20 1998 |
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics