# Subcellular Proteomic Investigation of Projection Neuron Growth Cones in Developing Mouse Cortex

> **NIH NIH F31** · HARVARD UNIVERSITY · 2024 · $33,742

## Abstract

Project Summary/Abstract
 During development of the cerebral cortex, cortical projection neuron subtypes extend axons to innervate
distinct targets located at great distances (103-105 cell body diameters) from their nucleus-containing somata.
This precise navigation and circuit development is regulated by growth cones (GCs): subcellular compartments
at tips of growing axons that rapidly integrate extracellular signals to control development of neural circuits, then
mature into synapses. Since GCs respond rapidly to chemical cues, while hours/days are required to transport
molecules between GCs and their parent somata, GCs highly likely function semi-autonomously. Prior work has
also revealed that local protein synthesis and degradation pathways in GCs are required for responses to some
directional cues. However, function of most GC proteins in axon guidance and circuit development have not been
identified, and even less is known about subtype-specific roles of GC proteins. This proposal combines recently
developed subtype-specific GC purification with ultra-low-input proteomics to 1) investigate subtype-specific GC
proteomes at distinct developmental stages (pre- and post-midline crossing) to identify and functionally
investigate proteins with stage-specific roles, and 2) investigate subtype-specific proteomes of dysfunctional GCs
to identify and functionally investigate dysregulated proteins with critical roles in precise circuit wiring.
 These rigorous in vivo investigations will deepen understanding of subtype-, and stage-specific mechanisms
regulating subcellular proteostasis in GCs, and how these processes control axon pathfinding and formation of
synaptic circuitry in cortical projection neuron subtypes. The intersection of circuit formation and subcellular
proteostasis has substantial

## Key facts

- **NIH application ID:** 10892642
- **Project number:** 5F31NS127518-02
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Dustin Eliot Tillman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $33,742
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892642

## Citation

> US National Institutes of Health, RePORTER application 10892642, Subcellular Proteomic Investigation of Projection Neuron Growth Cones in Developing Mouse Cortex (5F31NS127518-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10892642. Licensed CC0.

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