# Hippo regulation of peripheral myelination and nerve repair

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $346,719

## Abstract

Abstract
In the vertebrate peripheral nervous system, Schwann cells (SCs) make myelin that insulates large axons and
allows rapid conduction of nerve impulses. Myelinating SCs possess the innate ability to demyelinate and
transform into repair SCs, which promote axonal regeneration and remyelination after traumatic injury.
Demyelination can also occur pathologically, and there are no effective treatments to promote or enhance
remyelination after injury or disease. Myelination during development is triggered by activation of several SC
membrane-associated proteins, and requires that the transcription factor Krox20 be in the nucleus. However,
we know little about how myelination signals move from the membrane to the nucleus during development and
even less about the signaling required for myelin maintenance and remyelination. YAP/TAZ are paralogous
transcriptional co-activator proteins with diverse cellular functions, known best as potent promoters of cell
proliferation. Their activity is regulated by nucleocytoplasmic shuttling: when nuclear, they are transcriptionally
active. We recently showed that in SCs, YAP/TAZ are nuclear and required for Krox20 expression, myelin
formation and maintenance, suggesting that YAP/TAZ shuttle signals from membrane to nucleus to regulate
myelination. These findings lead us to hypothesize that YAP/TAZ are a nexus for multiple signaling pathways
that lead to transcriptional activation of Krox20 and myelin genes, and which thereby regulate developmental
myelination, myelin maintenance, demyelination and remyelination. To test our hypothesis, we propose the
following Aims: 1) Determine if YAP/TAZ mediate demyelination and remyelination; 2) Identify upstream
regulators of YAP/TAZ in myelin formation and maintenance; 3) Determine how YAP/TAZ regulate
transcription of Krox20 and myelin genes. We will use unique and conventional in vitro and in vivo techniques,
including multiple lines of inducible transgenic mice and RiboTag translatome profiling. The proposed study
should significantly enhance our understanding of how SCs form, maintain and repair peripheral myelin. It is
also likely to provide important new insights into how to prevent demyelination or promote robust remyelination
in peripheral nerve diseases.

## Key facts

- **NIH application ID:** 9899337
- **Project number:** 5R01NS105796-03
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** YOUNG-JIN SON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,719
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899337

## Citation

> US National Institutes of Health, RePORTER application 9899337, Hippo regulation of peripheral myelination and nerve repair (5R01NS105796-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9899337. Licensed CC0.

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