# Fascin1 in Growth Cone Motility and Guidance

> **NIH NIH F31** · EMORY UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY:
 The formation of the brain’s intricate neural network begins in embryogenesis. Axon guidance is a critical
developmental stage in which precise wiring of the central nervous system is achieved when axonal fibers
connect with specific target cells. Errors in axon guidance can result in wiring defects that are associated with
neurological disorders including epilepsy. The tips of axons have highly motile structures called growth cones
that can sense and respond to extracellular guidance cues to direct axon migration. Growth cones depend on
actin-based structures called filopodia to sense their surrounding environment and detect external guidance
cues. The formation of filopodia is dependent on the bundling of parallel actin filaments by actin cross-linking
proteins including Fascin1. During the guidance response, growth cone filopodia undergo remodeling, stabilizing
in the direction of attractive cues and collapsing in response to repulsive cues. I hypothesize that the loss of
Fascin1 in developing hippocampal neurons will result in erroneous axon guidance due to an inability to regulate
filopodia remodeling. The studies proposed here will utilize molecular, cellular biology, and imaging techniques
to study the role and regulation of Fascin1 in axon growth cones using cultured rat hippocampal neurons and an
in vivo Drosophila model.
 In Aim 1.1, the effects of Fascin1 depletion via CRISPR-Cas9 editing on filopodia extension, persistence,
and retraction will be studied. Three different axon guidance assays will be utilized to determine if Fascin1
depletion alters the ability of growth cones to undergo the guidance response. Aim 1.2 will study the
spatiotemporal dynamics of Fascin1 in growth cones of cultured rat hippocampal neurons undergoing guided
migration and the regulation of neuronal Fascin1 by protein kinase C (PKC). Previous work established that
phosphorylation of Ser-39 of Fascin1 by PKC abrogates Fascin1’s filament bundling ability and I hypothesize
that PKC regulates growth cone filopodia stability during axon guidance via this role. Aim 2 uses a Drosophila-
based approach to study the role of Fascin1 in axon guidance in vivo. Drosophila express an single ortholog of
mammalian Fascin1 called Singed and my preliminary studies indicate that the presence of Singed is required
for proper formation of the mushroom body, a neuronal structure that is dependent on axon guidance to form.
The studies proposed here will further the knowledge of cytoskeletal regulation during axon guidance which is
of importance due to the association of errors in axon guidance with neurological disorders, including epilepsy.

## Key facts

- **NIH application ID:** 11005686
- **Project number:** 5F31NS127574-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Katherine Rebecca Hardin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-05-15 → 2025-05-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11005686

## Citation

> US National Institutes of Health, RePORTER application 11005686, Fascin1 in Growth Cone Motility and Guidance (5F31NS127574-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11005686. Licensed CC0.

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