# Polarity, growth, and morphogenesis of epithelia

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $819,706

## Abstract

Epithelia are the core cell type of animals, and constitute the most widespread and ancient mode of tissue
architecture. Defects in epithelial organization, growth, or morphogenesis underlie a variety of medically
devastating disorders, from birth defects to cancer. To understand the biology of humans as well as the rest of
the animal kingdom, we need to understand how epithelia take on their distinctive form and how this form enables
function. My lab uses a distinctive set of multidisciplinary strategies to investigate these questions in Drosophila,
leveraging the deep evolutionary conservation of epithelial biology to uncover general principles applicable
across phylogeny. The research described in this MIRA application tackles three fundamental problems of
epithelial biology, ranging from the cellular to the tissue and organ scales.
First, how are epithelial cells polarized into complementary apical and basolateral domains? Our previous work
defined the Scribble module as a basolateral regulator that antagonizes the apical Par complex, but basic
questions of the role, relationship, and effector partners of the Scrib proteins remain unanswered, as are the
molecular mechanisms that link polarity regulators to the core cellular trafficking machinery. Second, what
mechanisms couple growth control in epithelial tissues to cell polarity? We and others have shown that polarity
disruption by genetic or physical means activates mitogenic signaling, suggesting that epithelial integrity is an
intrinsic control system used to maintain proper size and ensure repair. But how breaches in epithelial
homeostasis are detected to trigger proliferation is not understood. Third, how do 3D, multicomponent organs
acquire their distinctive shapes? Current paradigms emphasizing cell-autonomous Myosin II contractility derive
from analyzing 2D cellular sheets. By studying a simple 3D tube-like organ, we have uncovered multiple novel
phenomena including a new morphogenetic movement and an unappreciated mechanism for organ shaping
involving extracellular matrix stiffness. Major gaps exist in understanding how cellular and extracellular forces
are integrated to drive specific cell behaviors; our expertise uniquely positions us to close these gaps and
approach an in toto understanding of organ morphogenesis.
The proposed experiments tackle these questions by combining the traditional strengths of Drosophila genetics
with new tools with advanced imaging, collaborations with physical scientists, and the development of novel
experimental systems. Our results will enhance our understanding of the conserved mechanisms that generate
functional epithelial organs during development, and may provide new insights into diseases of epithelial origin.

## Key facts

- **NIH application ID:** 9843682
- **Project number:** 5R35GM130388-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** David Bilder
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $819,706
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843682

## Citation

> US National Institutes of Health, RePORTER application 9843682, Polarity, growth, and morphogenesis of epithelia (5R35GM130388-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843682. Licensed CC0.

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