# Mechanism of Growth Cone Turning in Diffusible Gradients

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $103,411

## Abstract

Project Summary
 Precise wiring of the nervous system depends on the guided growth of axonal
fibers to their specific targets for synaptic connections. Axon pathfinding depends on the
motile growth cone at the tip of developing axons, which senses and responds to a
variety of extracellular signals to navigate through a complex and changing environment.
The proposed study aims to elucidate a novel signal amplification mechanism that
enables growth cones to sense shallow gradients of guidance cues to generate highly
polarized actin-based motility. The work will take advantage of a well-defined neuronal
culture system for growth cone turning assays, sophisticated high-resolution imaging
techniques, direct manipulation of intracellular molecules, and molecular and
pharmacological manipulation of cellular components. The central hypothesis is that
phosphoinositide-based signal amplification enables the growth cone to sense shallow
gradients of guidance cues to generate directional responses. The proposed study will
further investigate the molecular mechanisms underlying the phosphoinositide-based
signal amplification. The goal is to gain a mechanistic understanding on how a growth
cone translates spatiotemporally distributed extracellular cues to distinct directional
responses, leading to the formation of specific synaptic connections.
 The cell’s ability to sense the environment and to determine the direction and
proximity of an extracellular stimulus, followed by correct movement, is fundamental for
many developmental events including neural development. Directed cell motility also
underlies many pathological events, especially cancer-cell metastasis. The proposed
study uses nerve growth cones as the model to study the signaling mechanisms that
underlie the directional sensing of growth cones during axon pathfinding. The results
from this study will not only provide significant insights into the molecular mechanisms of
axon guidance, but also extend our knowledge concerning directed cell movement in
many physiological and pathological events. Therefore the work is directly relevant to
public health.

## Key facts

- **NIH application ID:** 10135397
- **Project number:** 3R01GM083889-21S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** James Q Zheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $103,411
- **Award type:** 3
- **Project period:** 1998-08-20 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135397

## Citation

> US National Institutes of Health, RePORTER application 10135397, Mechanism of Growth Cone Turning in Diffusible Gradients (3R01GM083889-21S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135397. Licensed CC0.

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