# Dynamic polarity mechanisms controlling stem cell asymmetry during tissue development

> **NIH NIH F32** · STANFORD UNIVERSITY · 2020 · $60,855

## Abstract

PROJECT SUMMARY/ABSTRACT
 Cell polarity is necessary to pattern tissues and is essential in stem cells to generate cellular diversity
during development and homeostasis. Accordingly, polarity defects can drive developmental disorders and
diseases, including cancer. Previous studies have elucidated molecular mechanisms that generate polarity and
break symmetry in single cells. How these mechanisms are integrated to generate complex tissues remains
poorly understood. The stomatal lineage in the Arabidopsis leaf epidermis is an ideal system to quantitatively
determine how intrinsic cell polarity is transmitted to daughter cell asymmetry due to its well-characterized
developmental trajectory, optical accessibility, and genetic tractability. In this proposal, I will utilize the stomatal
lineage to 1) test how a novel microtubule-dependent inhibitory loop utilizes conserved logic to generate polarity
in stem cells and 2) delineate polarity-dependent mechanisms that drive daughter cell asymmetry. To accomplish
the proposed aims, I have developed novel in vivo tools to manipulate polarity in the stomatal lineage with high
temporal and subcellular precision. In Aim 1, I will use targeted depletion, molecular genetics, and high-resolution
imaging to test how mutual inhibition between microtubules and cortical polarity proteins generate a single
polarity axis in multipotent stem cells. Additionally, I will use quantitative in vivo imaging to experimentally test
how integrating an inhibitory circuit with a parallel MAPK-dependent positive feedback loop increases polarity
robustness. In Aim 2, I will leverage the strengths of the stomatal lineage to determine how stem cell polarity
regulates differential daughter cell size. By acutely manipulating polarity and tracking resulting daughter cell size,
growth, and fate decisions using long-term time-lapse microscopy in vivo, I will directly test how polarity regulates
downstream asymmetry. Furthermore, by identifying novel polarity regulators in the stomatal lineage, I will
identify molecular pathways that link polarity to differential daughter growth. Completion of the proposed aims
will test polarity models during multicellular development and will identify the mechanisms linking polarity to stem
cell asymmetry. Elucidation of polarity mechanisms in an evolutionarily divergent species has broad implications
for polarity models and may define synthetic strategies to correct polarity defects in human disease states.

## Key facts

- **NIH application ID:** 9964498
- **Project number:** 5F32GM133102-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Andrew D Muroyama
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $60,855
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964498

## Citation

> US National Institutes of Health, RePORTER application 9964498, Dynamic polarity mechanisms controlling stem cell asymmetry during tissue development (5F32GM133102-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9964498. Licensed CC0.

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