# Cytoneme-mediated hedgehog signaling in cardiac development

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $65,310

## Abstract

Project Summary / Abstract
Hedgehog (Hh) signaling is a critical initiator of developmental patterning in many tissues and organs including
the heart. Beyond development, Hh signaling acts to promote angiogenesis and epicardial regenerative capacity,
preserve function after myocardial infarction, and maintain coronary vasculature in adult myocardium. Cardiac
development requires trans-tissue Hedgehog signaling that is specifically received by a subset of cardiac
mesodermal cells. This study will test whether Hedgehog is transported by specialized signaling filopodia known
as cytonemes from the embryonic ectoderm to its target cells. Cytonemes are thin actin-based filopodia which
connect paracrine signal producing cells to receiving cells. Cytonemes have been shown to be the mechanism
by which morphogens are dispersed in many other developmental systems but have never been specifically
examined in cardiac development. We hypothesize that cytonemes extending between the dorsal ectoderm and
cardioblasts are responsible for the specificity of Hh distribution. The presence, function and necessity of Hh-
carrying cytonemes for cardiac tube development will be assessed using live confocal imaging of embryos which
express fluorescently tagged CD4 and Hh in the Drosophila embryonic ectoderm, mesoderm, or cardioblasts.
To further examine how cytonemes distribute Hh, electron microscopy (EM) will be used in the Drosophila larval
imaginal wing disc, where cytonemes have been well-established. Because cytonemes share some
characteristics of neurons, we will test whether a bouton structure is found at the junction between cytonemes
and their target cells. EM imaging will also be used to answer whether cytonemes connect to multiple or single
cells, and how Hh is transported along the cytonemes (e.g. membrane associated exosomes, intracellular
membrane, endocytic vesicles). Identification of cytoneme-mediated Hh delivery during cardiac development
would expand the way in which we understand and potentially target congenital heart defects, and influence
future approaches in regenerative medicine.

## Key facts

- **NIH application ID:** 9933823
- **Project number:** 5F32HL147624-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Brent Malcolm Wood
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933823

## Citation

> US National Institutes of Health, RePORTER application 9933823, Cytoneme-mediated hedgehog signaling in cardiac development (5F32HL147624-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9933823. Licensed CC0.

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