# How do glia remodel the nervous system?

> **NIH NIH F31** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $46,752

## Abstract

Project Summary
A common feature of nervous systems is that they are initially overpopulated with neurons and over-wired, initially
generating an excessive number of synaptic connections. This is followed by an essential period of remodeling
whereby a subset of extraneous neurons or synaptic connections are removed in order to optimize function in
the adult nervous system. The elimination of cells and pruning of synapses is a process coordinated by neurons
and glia. The selection of specific connections or cells for elimination seems to involve a conversation between
neurons and glia, and the clearance of debris from the nervous system is performed predominantly by phagocytic
glial cells. Previous research has highlighted that the nervous system uses a diversity of molecules and
mechanisms to identify engulfment targets, which appear to be context-specific. However, major gaps still exist
in our knowledge of how neurons identify themselves to be remodeled and how glial cells recognize these dying
or pruning neurons. Studying these processes can potentially lead us to a better understanding of mechanisms
underlying neurodevelopmental disorders such as Autism Spectrum Disorders and Schizophrenia. Our lab has
employed Drosophila as a model system for several reasons including the powerful genetic tools and the
stereotyped nature of one of its remodeling periods—metamorphosis. Through transcriptomic profiling in
phagocytic astrocytes, I identified the transmembrane immunoglobulin superfamily gene borderless. My
preliminary data suggests that Bdl is highly expressed in astrocytes during engulfment periods early in
metamorphosis. Interestingly, loss of both Borderless (Bdl) and the known engulfment receptor Draper (MEGF10
in mammals) resulted in strong suppression of astrocyte engulfment of synapses and neurites. Bdl has been
described to interact with a closely related protein named Turtle, and my preliminary data further suggests Turtle
is specifically localized to neurites and synapses, and excluded from the cell body (the only compartment of the
cell that astrocytes do not engulf). Turtle may therefore act as a molecular tag for astrocytes to recognize
appropriate engulfment targets. In Aim 1 of this study, I will characterize Bdl expression in astrocytes, explore
genetic interactions between Bdl and Draper, and determine which domains of Bdl are essential for engulfment
activity. In Aim 2, I will 1) define genetic interactions between Bdl, Turtle, and Draper, 2) determine the cell
autonomy of Bdl and Turtle in the remodeling of corazonin neurons and 3) determine the subcellular localization
of Turtle positing me to explore Turtle as a molecular tag for specifying neurites for engulfment. My work has the
potential to define two novel components of the astrocytic engulfment machinery, (Bdl and Turtle), explore how
they converge with Draper/MEGF10, and identify Turtle as a neurite/synapse-specific molecular tag that directly
directs astrocyte engulfm...

## Key facts

- **NIH application ID:** 10464236
- **Project number:** 1F31NS127557-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Rachel Yvette De La Torre
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-04-06 → 2024-10-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464236

## Citation

> US National Institutes of Health, RePORTER application 10464236, How do glia remodel the nervous system? (1F31NS127557-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464236. Licensed CC0.

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