# Molecular pathways regulating astrocyte morphogenesis and function

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $490,729

## Abstract

SUMMARY
Astrocytes are the most abundant glial cell type in the human brain and are critical for central nervous system
(CNS) development and function. Mature astrocytes are unusually elaborate cells, with an intricate and
ramified morphology. Their numerous fine cellular processes interact closely with synapses, neuronal cell
bodies, axons, blood vessels, and other glial cells throughout the CNS. Through these interactions, astrocytes
fulfil diverse functions to support and enhance neuronal activity, maintain CNS homeostasis, and modulate
circuits. Underscoring the importance of proper astrocyte development, defects in astrocyte growth or loss of
astrocyte complexity are implicated in many neurological diseases, including Alexander's disease, autism, and
epilepsy. However, it remains poorly understood how astrocytes develop their intricate morphological
associations and regulate neural circuit function.
Our long-terms goals are to understand how astrocyte acquire their remarkable morphology, target their
processes to synapses, and use these cell-cell contacts to modulate brain function. We recently performed a
genetic screen in Drosophila to identify new regulators of astrocyte development, and uncovered a novel gene,
Trapped in endoderm 1 (Tre1), as required for astrocyte morphogenesis. We find that loss of Tre1 leads to
severely reduced astrocyte complexity in vivo, resulting in decreased infiltration of the synaptic neuropil. Tre1
encodes a G protein-coupled receptor (GPCR) with no known function in the CNS. This proposal will use a
synergistic combination of molecular-genetic tools available in Drosophila and zebrafish along with new tools
we have generated and in vivo imaging to: determine how Tre1 regulates astrocyte morphogenesis, function,
and animal behavior in Drosophila (Aim 1); elucidate signaling pathways upstream and downstream of Tre1
activation (Aims 1+2); and define the evolutionary conservation of Tre1 in vertebrates (Aim 3). Our work will
provide exciting new insights into the mechanisms regulating astrocyte development and function in vivo and
lay the foundation for understanding astrocyte growth and dysfunction in human disease.

## Key facts

- **NIH application ID:** 10454296
- **Project number:** 5R01NS124146-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Marc R Freeman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $490,729
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454296

## Citation

> US National Institutes of Health, RePORTER application 10454296, Molecular pathways regulating astrocyte morphogenesis and function (5R01NS124146-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10454296. Licensed CC0.

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