# Piezo1 in neural stem cell mechano-regulation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $427,590

## Abstract

Mechanical signals are an important influence on the development, structure, and function
of the central nervous system. Neural stem/progenitor cells (NSPCs), which generate neurons,
astrocytes, and oligodendrocytes, are particularly sensitive to mechanical cues. During
development, mechanical signals drive NSPC lineage specification, cell migration, and axon
guidance. In stem cell transplant therapy, mechanical cues experienced by stem cells both in vitro
before transplantation and in vivo after transplantation influence engraftment. Despite their
manifest importance, the processes by which NSPCs detect, transduce, and generate mechanical
forces remain poorly understood. Our overall objective is to uncover novel molecular mechanisms
underlying NPSC mechano-regulation that could be harnessed for therapeutic strategies against
neurodevelopmental and neurodegenerative diseases.
We recently reported that the mechanically-activated ion channel Piezo1 generates Ca2+
flickers in NSPCs, and showed that its activity promotes differentiation into neurons rather than
glia. Our new preliminary data also shows that Piezo1 knockout in mice results in gross
abnormalities of the brain. Intriguingly, Piezo1 is active even in the absence of externally-applied
mechanical force and this activity is triggered by cellular traction forces – intracellular forces
generated by the cell’s acto-myosin cytoskeleton to probe mechanical properties of the
extracellular matrix. Here we examine the functional dynamics between traction forces and Piezo1
in NSPCs. Aim 1 examines how traction forces activate Piezo1; Aim 2 asks whether Piezo1
activity feeds back to modulate Myosin II activity; and Aim 3 examines the role of the mechanical
signaling between Piezo1 and Myosin II in neural tissue mechanics during development. These
studies will provide a mechanistic insight into Piezo1’s role in regulating NSPC behavior in vitro
and in vivo.

## Key facts

- **NIH application ID:** 9971603
- **Project number:** 5R01NS109810-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Medha M Pathak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,590
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971603

## Citation

> US National Institutes of Health, RePORTER application 9971603, Piezo1 in neural stem cell mechano-regulation (5R01NS109810-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971603. Licensed CC0.

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