# Mechanisms of Ventricular Wall Morphogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $497,783

## Abstract

PROJECT SUMMARY
Illuminating how the multi-layered ventricular wall is created entails investigating the earliest cellular events
that control the allocation of cardiomyocytes between these wall layers. Because its complex vertebrate
embryonic heart is comprised of 200-300 cardiomyocytes during cardiac chamber formation and furthermore is
amenable to high resolution in vivo live-imaging, the zebrafish embryo offers a unique opportunity to
interrogate in detail how individual cardiomyocytes dynamically organize to create the nascent structures of the
embryonic ventricular wall. As a result, recent zebrafish studies have shown that distinct cardiomyocytes
extend from the embryonic ventricular wall into the lumen to form cardiac trabeculae, whereas others remain
within this outer wall. Yet, how these cardiomyocytes are selected to form these distinct ventricular myocardial
wall layers still remains to be fully elucidated. Although previous studies have shown that endocardial Notch
signaling non-cell autonomously promotes myocardial trabeculation through Erbb2 and BMP signaling, we
have discovered a new and exciting role for myocardial Notch signaling within the ventricular myocardium to
coordinate the sorting of cardiomyocytes between the ventricular wall layers. Because Notch signaling has
been shown to control receptor tyrosine kinase (RTK) signaling through lateral inhibition pathways in order to
regulate the social interactions between cells that assign cell fate position during epithelial branching, we
hypothesize that a similar lateral inhibition mechanism between myocardial Notch and Erbb2 signaling may
guide the selection, allocation and assembly of cardiomyocytes to morphologically create the distinct wall
layers of the ventricular chamber. To further explore this hypothesis, we propose to: 1) investigate the
underlying mechanisms regulating myocardial Notch signaling activity; 2) examine how myocardial Notch
signaling regulates ventricular cardiomyocyte allocation; and 3) explore how the myocardial Notch-Erbb2
signaling axis regulates the dynamic cellular events guiding the morphogenesis of the ventricular wall layers.!

## Key facts

- **NIH application ID:** 10125002
- **Project number:** 5R01HL141508-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Neil C Chi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $497,783
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10125002

## Citation

> US National Institutes of Health, RePORTER application 10125002, Mechanisms of Ventricular Wall Morphogenesis (5R01HL141508-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10125002. Licensed CC0.

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