# Cell cycle dependent mechanisms triggering lumen formation in vivo

> **NIH NIH R01** · SYRACUSE UNIVERSITY · 2022 · $300,000

## Abstract

SUMMARY STATEMENT: In humans and other vertebrates, motile cilia located in an organ of asymmetry
play an important role in cardiac left-right development. Evidence from model organisms, such as in zebrafish
organ of asymmetry, (Kupffer’s Vesicle, KV) indicates that conserved cilia-driven leftward flow establishes left-
right signals to regulate target genes to control asymmetric heart morphogenesis. While events downstream of
leftward flow have received much attention, little is known about how the organ of asymmetry is formed and the
biology of the ciliated cells that generate fluid flow. This project addresses the broad question: How do ciliated
cells develop into a functional polarized organ? To address this question we are bringing together cell biology
and developmental biology to investigate how the cytokinetic bridge establishes apical polarity and a lumen in
vivo. We propose that this occurs through a sequential process that starts with cell division and placement of
the cytokinetic midbody, which marks a site for where the apical membrane should be placed. Cytokinetic
bridge resolution (a.k.a. abscission) results in the separation of two daughter cells following mitosis allowing for
the cell to initiate ciliogenesis. This process has important implications in embryogenesis, and broad
implications in the role of cytokinesis in developing cellular diversity. While abscission has been examined in
vitro, little has been done to examine the role of cytokinesis/abscission in epithelial establishment and de novo
lumen formation in vivo. Thus, our work will test the overall hypothesis that cell division is an essential
process that initiates lumen formation, ciliogenesis, and subsequently tissue morphogenesis. Here we propose
to examine in the zebrafish KV a requirement for abscission in the transition of progenitor-mesenchymal-like
migratory cells to epithelial-ciliated cells (tested in Aim 1). For instance, does cell division trigger KV-specific
apical polarity protein expression and does division contribute to how cells are patterned to form a KV? We
propose that following cytokinesis, daughter cells stay interconnected by a cytokinetic bridge while apical
polarity is established. This process requires targeted membrane traffic into the cytokinetic bridge. During this
time, the two daughter cells position themselves so that the cytokinetic bridge is placed where an apical
membrane and lumen will form. Once the bridge is cleaved, a lumen is initiated (Aim 2) and KV cells can form
primary cilia (Aim 3). We will use photoconversion to track cell fate following division, and laser ablation or
optogenetics to determine whether abscission timing is important for apical polarity, cilia formation, and
lumenogenesis. These studies will identify important mechanisms for de novo tissue morphogenesis.

## Key facts

- **NIH application ID:** 10322191
- **Project number:** 5R01GM130874-02
- **Recipient organization:** SYRACUSE UNIVERSITY
- **Principal Investigator:** Heidi Hehnly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $300,000
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322191

## Citation

> US National Institutes of Health, RePORTER application 10322191, Cell cycle dependent mechanisms triggering lumen formation in vivo (5R01GM130874-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10322191. Licensed CC0.

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