# Cell cycle control of cell polarity and fate in epidermal morphogenesis

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2024 · $438,058

## Abstract

Loss of cell polarity and invasive behavior are hallmarks of cancer, but how cell polarity is preserved
during tissue growth and turnover is poorly understood. Polarity refers to the asymmetric partitioning of
membrane components and subcellular structures, is oriented along both apicobasal and planar axes,
and is essential for the proper assembly and function of epithelial tissues. The preservation of cell polarity
is of crucial importance in tumor suppression and therefore, special mechanisms must exist to preserve
polarity when cells divide. We have shown that to preserve tissue architecture, epithelial polarity is
dynamically remodeled when cells divide. Asymmetrically localized polarity proteins are temporarily
removed from the cell surface via bulk endocytosis into the cytoplasm. After division, they are recycled
to the surface where polarity is restored. This mechanism is controlled directly by mitotic kinases, the
same machinery that controls cell cycle progression and is deregulated in cancer. Thus, cell division and
planar cell polarity are controlled by the same regulatory machinery, and may explain why, in cancer,
hyperproliferation and cellular disorder are so closely intertwined.
 In this proposal we build and expand on this foundational work to investigate how cell polarity is
restored after mitosis and how cell division facilitates the establishment of robust and aligned tissue
polarity. We will capitalize on our recent technical advancements in live and super-resolution imaging of
the skin to 1) decipher the transport mechanisms that restore polarity following mitosis and how mitotic
repolarization establishes tissue-scale polarity; 2) define the spatial cues that direct mitotic repolarization;
and 3) determine how neighboring cells coordinate mitotic removal of intercellular junctions via
transendocytosis. Successful completion of ours aims will uncover the mechanisms by which a highly
proliferative epithelium preserves tissue integrity.

## Key facts

- **NIH application ID:** 10788433
- **Project number:** 5R01AR068320-07
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Danelle N Devenport
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $438,058
- **Award type:** 5
- **Project period:** 2023-02-16 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10788433

## Citation

> US National Institutes of Health, RePORTER application 10788433, Cell cycle control of cell polarity and fate in epidermal morphogenesis (5R01AR068320-07). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10788433. Licensed CC0.

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