# Slit Fragments Generate Diversity in Axon Guidance Signals

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 2021 · $408,198

## Abstract

Axon guidance is the study of how developing nerves navigate in response to external
signals. A remarkably small number of navigational signals have been identified, raising
the question of how the complexity of the brain is generated. One solution is that a single
ligand can signal in different ways either through the presence of different receptors or
through processing that alters receptor binding. Slit is a large secreted protein that
typically repels growing axons using Robo receptors. Slit is cleaved into two fragments,
Slit-N and Slit-C, which display new biological activities in the nervous system and that in
many other tissues. However, the role of the Slit fragments is controversial. The Slit-N
fragment contains the Robo binding site and has been shown to be repel axons in in
vitro culture systems and so is thought to be the active signaling molecule. Multiple lines
of in vivo preliminary evidence in Drosophila suggest that only the full-length (Slit-FL)
protein repels axons. This proposal takes an in vivo molecular genetic approach in flies
and mice to separate the signaling of Slit-FL from that of the Slit fragments.These two
systems will allow us to address the effects of Slit on axon growth, axon branching and
regulated adhesion (fasciculation). This work will allow us to determine how a single
signal can achieve different biological outcomes. The proposed work has implications for
a diverse range of fields, including infectious disease, cancer and nerve regeneration.

## Key facts

- **NIH application ID:** 10052470
- **Project number:** 1R01NS114219-01A1
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** Thomas Kidd
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $408,198
- **Award type:** 1
- **Project period:** 2021-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052470

## Citation

> US National Institutes of Health, RePORTER application 10052470, Slit Fragments Generate Diversity in Axon Guidance Signals (1R01NS114219-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10052470. Licensed CC0.

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