# Mechanotransduction in morphogenesis of mucociliary epithelium and multiciliated cells

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2024 · $403,750

## Abstract

Abstract
Every time we breathe, we inhale toxins and pathogens. The mucus produced in our airway traps these
pathogens. Thousands of multiciliated cells (multiple cilia per cell, MCCs) line the epithelium of our airway work
in a synchronized fashion to propel the mucus upwards and out of our body. This coordinated process is
known as mucociliary clearance, which prevents pathogens from moving to our lungs and causing irreparable
damage. Despite the central role MCCs play in mucociliary clearance, our understanding of the morphogenesis
of MCCs in the context of mucociliary epithelium remains incomplete. For example, the assembly of too many
or too few cilia is associated with impaired MCC function and can lead to pathological outcomes. However, the
mechanisms that define the cilia number remain unaddressed. Using an in vivo model of Xenopus embryonic
epidermal MCCs, we recently discovered that the centriole number depends on the apical area of the cell.
Moreover, we demonstrated that mechanical tension that affects the apical area of MCCs also calibrates
centriole number via mechanosensitive (MS) ion channel Piezo1. Our results have raised many important
questions about the mechanisms of Piezo1 function in MCCs. Also, they strongly suggested that
mechanotransduction plays a central role in the morphogenesis of mucociliary epithelia, specifically MCCs.
This proposal will focus on elucidating the role of mechanical forces and mechanotransduction pathways in
determining the centriole number and apical area of MCCs and non-MCCs using three complementary
approaches. First, we will take a gene-specific approach to examine the role of Piezo1 in centriole number
control. Second, we will take a cellular biomechanics approach to understand the interaction between tissue-
scale and cell-intrinsic forces in determining the apical area of MCCs and non-MCCs. Third, we will use a
systems approach to identify other MS genes involved in MCC morphogenesis. Our long-term goal is to
elucidate the mechanisms that define the properties of individual organelles (e.g., size and number of cilia) and
how they relate to the architecture of cells (e.g., apical size, cilia organization) and the mucociliary tissue
(arrangement of MCCs and non-MCCs) to generate efficient fluid flow.

## Key facts

- **NIH application ID:** 10928134
- **Project number:** 5R35GM146856-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Saurabh S Kulkarni
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $403,750
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928134

## Citation

> US National Institutes of Health, RePORTER application 10928134, Mechanotransduction in morphogenesis of mucociliary epithelium and multiciliated cells (5R35GM146856-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10928134. Licensed CC0.

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