# Regulation of the Neuronal Transcriptome and Translatome by Myelination

> **NIH NIH F31** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $39,034

## Abstract

Project Summary
During peripheral nerve development, reciprocal interactions between axons and Schwann cells (SCs) regulate
the striking morphological and phenotypic changes in both cells required for the assembly and function of
myelinated axons in action potential propagation. Axons drive SCs to differentiate and form myelin sheaths
whereas myelinating SCs drive the re-organization of axons into polarized domains essential for saltatory
conduction. While much is known about the instructive role that neurons play in the maturation of SCs during
myelination, surprisingly little is known about how SCs regulate the phenotypic changes that axons undergo as
a consequence of myelination. The latter requires profound changes in the expression and distribution of cell
adhesion molecules, ion channels, and an expansion of axon diameter due to alterations in the local axonal
cytoskeleton, and a new reliance on SCs for trophic and metabolic support. The extent to which these phenotypic
changes are mediated by transcriptional changes, translational changes, or post-translational changes, remains
poorly understood. Recently there has been a growing appreciation for the role of translation as a key regulatory
node in gene expression. This can be explored through analysis of the translatome, which refers to all mRNAs
recruited to ribosomes for protein synthesis. Given the striking effects that SCs have on the local structure and
function of the axons they myelinate, and given the important role of local translation in regulating protein
expression, I hypothesize that myelination significantly alters neuronal protein expression at the level of the
translatome. To test this directly, I employed translating ribosome affinity purification (TRAP)-based translatome
profiling as a way to isolate pools of actively translating mRNAs in neurons. I generated PVCre; Rpl22HA mice,
which express hemagglutinin (HA)-tagged ribosomal protein (Rpl22) in parvalbumin (PV)+ neurons, enabling
isolation of ribosome-associated transcripts specifically in PV+ dorsal root ganglion (DRG) neurons with minimal
contamination from glial or other transcripts. Using this approach, I carried out translatome profiling of DRG
neurons from myelinated and amyelinated mice. My preliminary data has revealed there are distinct pools of
transcripts enriched in the translatomes of myelinated vs. amyelinated neurons, and furthermore that the
translatomes of amyelinated neurons may be depleted in genes associated with mitochondria and metabolism,
thus raising the possibility that SC myelination may regulate mitochondrial biogenesis and function. My proposed
research plan aims to (1) elucidate the extent to which these observed myelination-dependent translatome
changes result from transcriptional regulation vs. translational regulation, and (2) determine what effect
myelination has on mitochondrial biogenesis and function. This work would provide a major, new insight into how
axo-glial interactions may re...

## Key facts

- **NIH application ID:** 10465670
- **Project number:** 1F31NS127539-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ashley Sartoris
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,034
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-12-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465670

## Citation

> US National Institutes of Health, RePORTER application 10465670, Regulation of the Neuronal Transcriptome and Translatome by Myelination (1F31NS127539-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10465670. Licensed CC0.

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