Our Focus:

​While adult mammals undergo scarring after spinal cord injury, zebrafish vigorously regenerate and completely recover motor function after a paralyzing injury. Key for this regenerative capacity are both neurogenesis and the formation of a tissue bridge between the two severed spinal cord stumps, composed of glial cells and nerve fibers (axons). Neonatal mice also regenerate axons after spinal cord injury, and recent studies have bolstered the idea of similar regeneration mechanisms to those in zebrafish.

We ask the following questions:
- What are the factors and mechanisms allowing innate spinal cord regeneration?
- How are these mechanisms regulated?
- Are there conserved pro-regenerative mechanisms between zebrafish and neonatal mouse spinal cord?
- Can regeneration in adult mammals be awaken by re-establishment of innate pro-regenerative mechanisms?

Overall, our goal is to contribute to the development of strategies to awaken spinal cord regeneration in adult mammals.

1. Regenerating Lost Neurons After Spinal Cord Injury

Spinal cord injury in adult zebrafish triggers proliferation of neural progenitors and their subsequent differentiation into new neurons that are able to integrate into the existing circuitry. We are exploring the cellular and molecular mechanisms controlling neural progenitors stemness, behavior and neurogenic potential by implementing new methods to image key subcellular, cellular and molecular events during regeneration.

2. Regrowing Severed Axons to Restore Motor Function

Motor function deficits after spinal cord injury are primarily due to disruption of rostro-caudal axonal connections. We are using profiling approaches, strategies to visualize neuronal connections in situ and regeneration assays to pinpoint signals required for regeneration of axon tracts severed after injury. While exploring how axons spontaneously regenerate and navigate the injury environment in zebrafish, we keep an eye open on how to use our discoveries in platforms to enhance regenerative capacity in adult mammals.

3. Elucidating Evolutionarily Conserved Spinal Cord Regeneration Responses

Our previous studies identified some zebrafish injury-responsive chromatin regions (regeneration enhancers) functionally conserved in mouse. Notably, for some of these zebrafish enhancers recognition and function are conserved in neonatal mice, able to regrow axons after spinal cord injury as the zebrafish, but not in adult mice undergoing scarring. We are using this knowledge to identify conserved mechanisms of spinal cord regeneration across species, whose re-establishment in adult mammals would possibly boost regeneration.