# Molecular correlates of proprioceptor subtype identity

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $354,375

## Abstract

Sensory modalities such as pain, touch, and proprioception serve a crucial role in conveying information
regarding the external and internal environment. Recent years have seen progress in defining the molecular
basis of nociceptor and touch receptor subtypes, but proprioceptor subtype diversity remains poorly
understood at both a cellular and molecular level. Proprioceptive muscle feedback is critical in the planning and
adjustment of motor output and derives from three main proprioceptor subclasses: group Ia and group II
muscle spindle (MS) afferents, and group Ib Golgi tendon organ (GTO) afferents. But, without genetic access
to the individual proprioceptor subtypes, their specific contributions to the execution of coordinated motor
movement remain unknown.
Proprioceptive sensory neurons (pSNs) extend axons to their peripheral muscle receptors shortly after
they establish a `generic' pSN identity. The prevailing view is that proprioceptor MS/GTO subclass identity is
determined at these early embryonic stages through intrinsic genetic programs. However, our recent studies
identified several transcripts that are preferentially expressed in subsets of proprioceptors after they innervate
their MS and GTO sensory organs. Moreover, for at least one of these transcripts expression appears to
depend on the presence of sensory receptors. Thus, while it is possible that these transcripts merely reflect
differences in MS/GTO afferent maturation, our findings have begun to question the notion that proprioceptor
MS/GTO subtype identity strictly depends on intrinsic transcriptional programs. Instead, we hypothesize that i)
proprioceptor subclass identity is acquired though a protracted process with a gradual induction and/or
selective maintenance of subclass specific transcripts, and ii) is in part induced by retrograde signals from their
peripheral sensory organs.
This proposal test these ideas through three sets of experiments. First, we will combine viral and
genetic strategies to assign a MS (group Ia/II) or GTO (group Ib) subclass identity to a selected set of
candidate proprioceptor subtype markers, and test the requirement of these molecules in proprioceptor
subtype acquisition. Second, we will take advantage of single cell transcriptome sequencing technologies to
delineate the molecular dynamics through which pSN MS/GTO subclass identities emerge during
development. Third, we will assess the role of extrinsic signaling molecules in directing pSN subclass identity.
 Together these studies will provide a comprehensive understanding of the molecular basis of
proprioceptor subclass identity, thus permitting renewed efforts to delineate the role of these important sensory
neurons in motor control at both a physiological and circuit level.

## Key facts

- **NIH application ID:** 9868335
- **Project number:** 5R01NS106715-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Joriene De Nooij
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,375
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868335

## Citation

> US National Institutes of Health, RePORTER application 9868335, Molecular correlates of proprioceptor subtype identity (5R01NS106715-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9868335. Licensed CC0.

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