# Secreted Factors for Zebrafish Spinal Cord Regeneration

> **NIH NIH R21** · DUKE UNIVERSITY · 2022 · $201,250

## Abstract

Primary and secondary tissue damage from spinal cord injury permanently impairs sensory and motor functions,
causing irreversible paralysis. Developing therapies to treat and reverse spinal cord injury is an urgent need in
regenerative medicine and remains an enormous research challenge. The path to an effective cure requires a
combination of molecular, cellular, electrostimulatory, and engineering approaches, and must be guided by a
deeper understanding of the inherent regenerative capacity of spinal cord tissue. Following spinal cord injury,
nerve cell death and scar formation inhibit regeneration. To date, attempts to alleviate the negative effects of
scarring and to support cell survival and nerve regrowth after injury have not overcome the challenges of
mammalian spinal cord regeneration. By contrast with mammals, teleost zebrafish can form new neurons, regrow
axons, and recover the ability to swim just 6 to 8 weeks after a paralyzing injury that completely severs the spinal
cord. Importantly, these regenerative events proceed without massive scarring. Instead, following injury,
specialized non-neural glia and other cells build a tissue bridge to connect the two severed ends, allowing axons
to grow across the wound and reestablish crucial connections. Encouraging key mammalian cells to adopt this
bridging behavior would shift the mammalian spinal cord injury response from scarring to regeneration,
potentially to an extent sufficient to save tissue function. This highly desirable outcome requires an extensive
understanding of the molecular signals that enable innate spinal cord regeneration. We have bioinformatically
assessed datasets of transcriptome changes after spinal cord injury in zebrafish and mice, with the idea that
factors preferentially induced in a successful context of regeneration would be instructive for such events. Based
on the preliminary data from analysis of several new mutant and transgenic zebrafish strains, we propose to: 1)
elucidate the roles of an induced and secreted factor in the regulation of spinal cord regeneration in zebrafish;
and 2) define the molecular regulation and targets of this factor after spinal cord injury. Our work will provide an
in-depth understanding of a key factor during spinal cord regeneration and reveal insights into its regulatory
mechanisms. These discoveries will guide approaches for comprehending, and potentially manipulating, the
capacity for human spinal cord regeneration.

## Key facts

- **NIH application ID:** 10338234
- **Project number:** 1R21NS124635-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** KENNETH D POSS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,250
- **Award type:** 1
- **Project period:** 2021-12-21 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10338234

## Citation

> US National Institutes of Health, RePORTER application 10338234, Secreted Factors for Zebrafish Spinal Cord Regeneration (1R21NS124635-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10338234. Licensed CC0.

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