NIH grant: PIEZO1-Mediated Mechanotransduction in Neural Development (1R01NS146326-01)

retained text

NIH grant 1R01NS146326-01: PIEZO1-Mediated Mechanotransduction in Neural Development
Institute: {'code': 'NS', 'abbreviation': 'NINDS', 'name': 'National Institute of Neurological Disorders and Stroke', 'admin_org_id': '12500053', 'admin_funding_url': ''}. PI: Medha M Pathak. Award: $621468.
Start: 2026-07-01T00:00:00.
Project Summary
Mechanical forces are essential for neural development, and their dysregulation leads to neurodevelopmental
defects. The mechanically-activated ion channel PIEZO1 plays critical roles in neural development, but the
mechanisms by which it detects and transduces mechanical signals into cellular responses remain poorly
understood. This proposal aims to elucidate how PIEZO1 mechanotransduction shapes early neural
development through three specific aims: (1) Decipher the mechanistic links between cell-generated forces,
membrane tension, and PIEZO1 in Neural Stem Cells (NSCs); (2) Determine the molecular mechanism
underlying PIEZO1-mediated regulation of cholesterol biosynthesis in neural development; and (3) Elucidate
the role of PIEZO1 in NSC and neuronal migration. The research employs innovative approaches including:
quantitative imaging of endogenous PIEZO1 activity using PIEZO1-HaloTag human induced pluripotent stem
cells, micropatterned substrates to control cellular mechanics, neural rosette models that recapitulate early
human neural development, genetically-engineered mice, and bioengineered scaffolds that mimic radial glial
tracks guiding neuronal migration. This systematic investigation spanning single molecules to developing
tissue models will reveal fundamental mechanisms by which PIEZO1 coordinates cellular responses to
mechanical cues during neural development. Understanding these pathways has therapeutic potential for
neurodevelopmental disorders where mechanical signal transduction is disrupted.

document fetched 2026-07-12 08:14