# The role of the glial engulfment receptor Jedi1 in regulating sensory neuron function

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $338,188

## Abstract

The dorsal root ganglia (DRG) are a diverse collection of sensory neurons that convey information such
as proprioception, mechanosensation and temperature from the periphery to the CNS. Stimuli that activate
specific DRG neurons (nociceptors) can trigger pain sensation. There is increasing evidence that satellite glial
cells (SGCs), which surround the DRG neurons, modulate sensory processing, particularly for chronic pain.
The overall objective of this project is to elucidate the mechanisms by which SGCs influence sensory neuron
function; particularly, how the engulfment receptor Jedi1, expressed by SGCs, regulates nociceptive neurons.
SGCs form a tight barrier around DRG neurons and buffer the local milieu, thereby regulating neuronal activity.
In addition, we demonstrated that SGCs are the primary phagocytes that clear apoptotic neurons during
development of the DRG and identified Jedi1 as a novel engulfment receptor expressed by these glia. To
investigate the in vivo role of Jedi1, we generated jedi1-/- mice. In the DRG from null mice the removal of dead
cells during development was impaired. Interestingly, despite Jedi1 expression only being detected in the glia
and not the neurons, we found altered function of jedi1-/- sensory neurons. Electrical recording from perinatal
jedi1-/- DRG neurons revealed a substantial increase in excitability; most wild type neurons only fired 1-2
action potentials in response to current injection, whereas most jedi-/- cells fired multiple action potentials.
Such enhanced excitability is typical of DRG neurons in early development and following nerve injury. The
hypersensitivity was accompanied by a 25% decrease in the number of DRG neurons in adult, but not perinatal
jedi1-/- mice, suggesting there may be excitotoxic neurodegeneration. In addition, there was a 30% increase in
the fraction of DRG neurons responsive to capsaicin, which was paralleled by enhanced capsaicin-induced
allodynia in jedi1-/- mice relative to wild type. Enhanced excitability, a greater fraction of capsaicin responsive
neurons and increased susceptibility to apoptosis, are all associated with DRG neurons in early development,
suggesting defects in the normal maturation of jedi1-/- neurons. Therefore, we hypothesize that loss of Jedi1
in SGCs results in impaired sensory neuron maturation, which leads to altered nociception and
excitotoxic neurodegeneration. To test this hypothesis, we will (1) determine which sensory modalities are
altered in jedi1-/- mice, (2) determine if loss of Jedi1 selectively in SGCs during development leads to an
altered sensory neuron phenotype, (3) identify the mechanism underlying the sensory neuron phenotype.
These studies will reveal fundamental mechanisms by which glia regulate neuronal function and sensory
perception, provide a foundation for understanding how dysfunctional signaling can lead to peripheral
sensitization and disease, and potentially identify novel targets for the treatment of chronic pain.

## Key facts

- **NIH application ID:** 9930670
- **Project number:** 5R01NS102365-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Bruce D Carter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $338,188
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930670

## Citation

> US National Institutes of Health, RePORTER application 9930670, The role of the glial engulfment receptor Jedi1 in regulating sensory neuron function (5R01NS102365-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9930670. Licensed CC0.

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