# Development of specific neuron-glia attachments

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $527,665

## Abstract

Abstract
 During development, cells adhere to specific partners in precise arrangements to build well-ordered
structures. Nowhere is this more impressive than in the brain, which has the most diverse cell types with
the most elaborate morphologies and most highly specific connectivity of any organ. While extensive
work has been done to identify mechanisms of partner selection among neurons, far less is known about
neuron-glia pairing. Glia extend membranous processes that intimately wrap specific synapses, affecting
synapse growth and pruning, and modulating synapse strength during learning. Defects in glia-neuron
interactions are associated with a host of neurodevelopmental disorders. Thus, understanding how
specific neuron-glia attachments are determined will shed light on a key aspect of brain wiring, and will
reveal general principles by which cells select specific adhesion partners during development.
 This project uses a single defined neuron-glia attachment as a model to identify the developmental
and genetic mechanisms that underlie neuron-glia pairing. It focuses on a single C. elegans sensory
neuron, called URX, that forms membranous attachments to a specific glial partner, the lateral ILso glial
cell. Highly cell-type-specific drivers allow this single, defined neuron-glia contact to be visualized or
genetically manipulated in live intact animals. Preliminary data show that this specific neuron-glia
attachment arises in embryos by a multi-step developmental process. First, the URX dendrite anchors to
a 'guidepost' glial cell during embryo elongation, positioning the dendrite ending at the nose tip. Then, a
sensory cilium grows out of the dendrite tip to form the elaborate attachment to the ILso glial partner.
 This project will investigate:
 Aim 1. How does the dendrite anchor to the guidepost cell? Preliminary data suggest that epithelial
adherens junctions are modified to create the anchoring site.
 Aim 2. How does the sensory cilium mediate neuron-glia adhesion? Preliminary genetic screens
have identified several mutants that disrupt cilia adhesion, including one that affects a proteoglycan with
homology to a protein that mediates glia-synapse interactions in mammalian brain.
 Aim 3. What is the function of this highly specific neuron-glia attachment? Preliminary work indicates
that the attachment undergoes experience-dependent remodeling, suggesting a mechanism by which
glia could tune the sensitivity of the neuron by altering the physical structure of its receptive ending.

## Key facts

- **NIH application ID:** 10802925
- **Project number:** 2R01NS112343-05
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Maxwell Heiman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $527,665
- **Award type:** 2
- **Project period:** 2019-07-15 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802925

## Citation

> US National Institutes of Health, RePORTER application 10802925, Development of specific neuron-glia attachments (2R01NS112343-05). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10802925. Licensed CC0.

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