# Transcriptional regulatory mechanisms of vertebrate regeneration

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $391,387

## Abstract

SUMMARY
In many species, spinal cord regeneration is driven by the proliferation and differentiation of neural progenitor
cells (NPCs), but therapeutic efforts to promote regeneration in human patients through engraftment of neural
stem cells or progenitor cells have had limited success. These limitations arise in part because the cell-intrinsic
properties of NPCs and neurons that enable natural regeneration are still largely undefined, as are the spatial
cues that confer positional identity on these cells in a regenerative context. Tadpoles of the frog Xenopus
tropicalis can respond to major spinal cord injury with scarless healing and regeneration, a capability that is lost
as the tadpole completes metamorphosis. This stage-specific regenerative competence represents a uniquely
sensitive system in which to define the transcriptional regulatory profile of NPCs and neurons that support
regeneration, and the incremental changes in all spinal cord cells that contribute to regenerative loss. In this
project, we will test the central hypothesis that regenerative competence is dictated by the ability of NPCs to
respond to injury by transcriptionally activating spatiotemporally distinct programs of proliferation or neuronal
subtype differentiation. Our project examines this hypothesis from three standpoints. First, we will ask how the
spatial organization of the spinal cord, and specifically NPC domains, is re-established after injury, explicitly
asking whether embryonic patterning cues along the dorsal-ventral axis are recapitulated. Second, we will
define the functions of two new transcriptional regulators of spinal cord regeneration that we have identified,
Pbx3 and Meis1, identifying the gene targets, sensitive cell types, and protein interactions of these two TALE
box transcription factors contrast between embryonic development and regeneration. Finally, we will test
specific hypotheses for how regeneration fails by contrasting the cell intrinsic changes in NPCs and neurons
that occur in response to injury in regenerative versus non-regenerative stages. By completing this project we
will fundamentally advance our understanding of how regeneration is achieved and how it is lost in this closely-
related vertebrate, opening the door for new therapeutic strategies informed by this naturally occurring model
of regeneration.

## Key facts

- **NIH application ID:** 10757641
- **Project number:** 5R01NS099124-07
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Andrea Elizabeth Wills
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $391,387
- **Award type:** 5
- **Project period:** 2017-07-15 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757641

## Citation

> US National Institutes of Health, RePORTER application 10757641, Transcriptional regulatory mechanisms of vertebrate regeneration (5R01NS099124-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10757641. Licensed CC0.

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