# Developmental Dynamics of Ciliated Epithelia

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $329,248

## Abstract

Project Summary:
The directed beating of motile cilia is a critical aspect of tissue function in a variety of developmental and
physiological contexts including proper neural development, egg migration through the oviduct and mucus
clearance in the respiratory tract. The loss of cilia motility results in a wide range of phenotypes including
hydrocephaly, infertility, situs inversus, and respiratory dysfunction. We have developed the ciliated epithelium
of Xenopus larval skin as a model system to ask: How do ciliated cells generate, maintain and ultimately
destroy hundreds of cilia and how do they orient those cilia in an organized way? We have developed
numerous light microscopic methods for visualizing specific aspects of ciliated cells in the developing skin of
Xenopus embryos. Specific to this application we have implemented the use of LITE sheet microscopy. These
methods will allow us to visualize the massive centriole duplication required to generate the approximately 150
basal bodies that nucleate the cilia with significantly improved temporal resolution. Additionally, we can visualize
and accurately quantify the cytoskeletal interactions that facilitate the establishment of cilia orientation. Using
these methods we will address: (1.) Regulation of cytoskeletal dynamics during the polarization of ciliated
epithelia, (2.) The regulation of centriole amplification, and (3.) The transdifferentiation of MCCs. Our
results will provide an important link between polarity cues, hydrodynamic forces and the regulation of
cytoskeletal dynamics during cellular polarization. Additionally, we will continue our efforts to understand the
regulation of centriole biogenesis but expand this work to include the scaling mechanism that regulate centriole
number. Finally, we will develop the MCCs of Xenopus as a novel model to understand the molecular regulation
of transdifferentiation. While our work is focused on ciliated epithelia, the cell and developmental mechanisms
we discover will be broadly applicable. The connection between cytoskeletal dynamics and cell polarity is widely
accepted in numerous developmental and disease contexts, and our experiments will likely uncover both MCC
specific and more general mechanistic features of this connection. Additionally, defects in centriole duplication
highly correlate with late stage cancer progression, indicating an uncoupling of duplication from normal cell cycle
progression. The cellular process of transdifferentiation is important during regeneration and cancer
progression. Our experiments will provide important developmental control over this process allowing us to
uncover novel aspects of coupling transcriptional regulation and autophagocytic recycling.

## Key facts

- **NIH application ID:** 10237937
- **Project number:** 5R01GM089970-12
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** BRIAN Joseph MITCHELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $329,248
- **Award type:** 5
- **Project period:** 2010-04-02 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10237937

## Citation

> US National Institutes of Health, RePORTER application 10237937, Developmental Dynamics of Ciliated Epithelia (5R01GM089970-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10237937. Licensed CC0.

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