# Cellular and Molecular Mechanisms Underlying Neuronal Type-specific Axon Regeneration

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $406,188

## Abstract

Project description
 Failure in axon regeneration after nervous system lesion is a major roadblock for
functional recovery. Axon regeneration is controlled by both intrinsic and extrinsic cues
from both neurons and surrounding glial environment. However, our understanding of
glial control of axon regeneration remains incomplete. Here, we investigate axon
regeneration of well-defined sensory neurons in Drosophila larvae. This in vivo model
offers a powerful opportunity to investigate axon regeneration with single-cell resolution
and genetic tractability. Our pilot study has made novel findings by discovering a critical
involvement of glia-neuron interactions, in the form of gliotransmission, in specifying
axon regenerative differences of neuron types. Based on these findings, we hypothesize
that gliotransmission orchestrates neuron type-specific axon regeneration. Specifically,
we propose that axotomy activates Ca2+ signals in glial cells to elicit gliotransmission,
leading to accumulation of extracellular ATP. ATP is then converted by ecto-5’-
nucleotidases to adenosine before activating adenosine receptors in the select neuron
type, resulting in neuron type-specific Ca2+ signals and axon regeneration. In this project,
we will leverage the power of Drosophila genetics and combine it with multidisciplinary
approaches to test this hypothesis. Because axon regeneration mechanisms are
conserved, our findings will likely be relevant to other species including mammals.

## Key facts

- **NIH application ID:** 10775747
- **Project number:** 5R01NS126821-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Yang Xiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $406,188
- **Award type:** 5
- **Project period:** 2023-02-06 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10775747

## Citation

> US National Institutes of Health, RePORTER application 10775747, Cellular and Molecular Mechanisms Underlying Neuronal Type-specific Axon Regeneration (5R01NS126821-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10775747. Licensed CC0.

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