Primary and secondary damage caused by spinal cord (SC) injury permanently impairs sensory and motor functions. Developing means to treat and reverse SC injury remains a pressing need in regenerative medicine. Approximately 10,000 Americans suffer new SC injuries each year, requiring long-term therapeutic, rehabilitative, and psychological interventions. With an average age of 33.4 years at the time of injury, the population of SC injury patients is steadily increasing in the United States and around the world. By contrast with mammals, teleost fish are capable of efficient, natural recovery after SC damage. Following SC transection, adult zebrafish initiate a glial bridge that re-connects the SC. Bridging is a striking gial cell response that is thought to provide a natural scaffold for axon growth. Importantly, glial bridging occurs in zebrafish without the detrimental outcomes from reactive gliosis that is elicited in mammalian SC injury contexts. However, little is known about the cells that construct the bridge and the molecules that enact bridge formation. Here, we propose to: 1) investigate the signaling pathways that drive glial bridging and SC repair in zebrafish; and 2) define the subpopulation of glial cells that construct the bridge. This study will provide a mechanistic understanding of glial bridging during zebrafish SC regeneration, information that will guide approaches for comprehending and manipulating mammalian regenerative capacity.
Our work will provide in-depth understanding of cells and molecules that direct glial bridging during spinal regeneration in zebrafish. These discoveries will guide approaches for comprehending and manipulating the molecular and cellular challenges to mammalian regeneration.
| Mokalled, Mayssa H; Poss, Kenneth D (2018) A Regeneration Toolkit. Dev Cell 47:267-280 |
| Chen, Chen-Hui; Poss, Kenneth D (2017) Regeneration Genetics. Annu Rev Genet 51:63-82 |
