# Regulating axon guidance through local translation at adhesions

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $56,442

## Abstract

PROJECT SUMMARY
The precise establishment of neuronal connectivity during development is critical for normal nervous system
function. This research examines how growth cones, which are the pathfinding structures of the developing
neuron, connect with their appropriate targets. External cues regulate neuronal connectivity formation by
resulting in the activation of intracellular signaling pathways and ultimately, reorganization of the cytoskeleton
and adhesions. This proposal focuses on understanding the molecular mechanisms linking extracellular
signaling with intra-axonal local translation in the developing nervous system. Local translation in axonal
growth cones is necessary for axon growth and guidance, however our understanding of how local translation
functionally directs axon guidance is limited. We recently demonstrated that point contacts, adhesion sites
within growth cones, are a strategic location for targeted local translation. Point contact adhesions directly
regulate axon guidance by linking the extracellular matrix to the intracellular actin cytoskeleton and providing
the force for growth cone movement. Thus, this finding is important because it suggests that local translation of
certain mRNAs at adhesions are situated to have a maximal impact on axon guidance. Point contacts are likely
a fundamental puzzle piece that has been missing from our understanding of how local translation functionally
directs axon guidance. Accordingly, our hypothesis is that local translation of β-actin mRNA is necessary
for point contact dynamics, and point contacts are localized organizing nodes for translational
regulation. We will test this hypothesis by determining if locally translated β-actin is integrated into point
contacts to direct axon guidance (Aim 1) and elucidating the signaling pathway through which extracellular
matrix-induced signaling stimulates intra-axonal mRNA translation (Aim 2). Furthermore, we will resolve the
suite of mRNAs that are locally translated in response to extracellular matrix proteins, and their relationship to
point contacts (Aim 3). Completion of the proposed aims will break new ground by discovering the interactions
between the extracellular matrix, point contacts and local translation in the regulation of axon guidance. This
research will enable a broad, mechanistic understanding as to how mRNA trafficking and local translation
contributes to the establishment of neuronal connectivity, and increase our knowledge about the complex
nature of brain development.

## Key facts

- **NIH application ID:** 10991766
- **Project number:** 3R01NS125146-02S1
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Kristy Welshhans
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $56,442
- **Award type:** 3
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10991766

## Citation

> US National Institutes of Health, RePORTER application 10991766, Regulating axon guidance through local translation at adhesions (3R01NS125146-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10991766. Licensed CC0.

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