# Mechanisms of Glial Interactions and Function at Neuronal Cell Bodies

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $1

## Abstract

PROJECT SUMMARY/ABSTRACT
All major mammalian glial subtypes of the central nervous system (CNS) make direct contacts with neuronal cell
bodies; however, how glia support and communicate with neuronal somas is vastly understudied compared to
glial interactions at synapses or axons. The overarching goal of this project is to gain a deep mechanistic
understanding of glial development, communication, and function at neuronal cell bodies to begin to fill in the
gaps of how these associations regulate CNS health and dysfunction. Drosophila glia demonstrate remarkable
similarity to a number of mammalian glial subtypes measured by morphological, functional, and molecular
criteria. Among these is cortex glia, a glial subclass that forms a lace-like meshwork to individually ensheath
nearly every neuronal cell body in the CNS. We recently developed new genetic tools to manipulate gene function
with remarkable specificity in Drosophila cortex glia, and now have a powerful system in which to study glial cell
development and neuron-glia interactions at neuronal cell bodies in vivo. In addition to regulating neuronal
health and behavior, cortex glia provide metabolic support to neurons, regulate neuronal ion and nutrient
balance, engulf neuronal debris, and can therefore inform the interrogation of multiple vertebrate glial cells that
interact with neuronal cell bodies.
We previously demonstrated that when cortex glia lack a single secreted neurotrophin, Spätzle 3 (Spz3), they
take on a globular appearance and no longer wrap neuronal cell bodies. The loss of Spz3 and these glial-somal
interactions leads to widespread nervous system dysfunction, including increased neuronal cell death, locomotor
impairment, and aberrant growth of surrounding healthy glial cells. We propose to use powerful in vivo genetic
tools available in Drosophila, along with a variety of techniques in cellular and molecular biology, biochemistry,
and imaging to elucidate the mechanisms of glial-somal interactions that maintain neuronal health in a live, intact
nervous system. Specifically, we will dissect the mechanisms that regulate the maturation and distribution of this
neurotrophin to maintain glial contact at neuronal cell bodies (Aim 1), define how this neurotrophin signals to its
receptor to support glial morphology, somal interactions, and neuronal health (Aim 2), and finally, we will
determine how nearby glial cells compensate when glial-somal signaling and associations are impaired (Aim 3).
These findings will begin to shed light on an understudied, yet important phenomenon by providing a foundation
for elucidating the cellular and molecular underpinnings of glial interactions with neuronal cell bodies in the
healthy and diseased CNS.

## Key facts

- **NIH application ID:** 10386883
- **Project number:** 5R01NS121101-02
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Jaeda Coutinho-Budd
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2021-04-15 → 2022-04-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386883

## Citation

> US National Institutes of Health, RePORTER application 10386883, Mechanisms of Glial Interactions and Function at Neuronal Cell Bodies (5R01NS121101-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10386883. Licensed CC0.

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