# Revealing the mechanisms of neural-mediated cardiac proliferation in Ciona robusta

> **NIH NIH F32** · SWARTHMORE COLLEGE · 2024 · $78,012

## Abstract

Project Summary/Abstract
Regulation of cardiomyocyte division is required for proper heart development, and is implicated in congenital
heart disease. Neural innervation of the heart regulates heart rate, which impacts cardiomyocyte proliferation.
Furthermore, neurons release neuropeptides that are key factors in promoting cell proliferation. Recent evidence
suggests neural innervation from the sympathetic and parasympathetic nervous system (extrinsic innervation)
of the heart promotes cardiomyocyte proliferation in post-natal mice. Ciona robusta are a closely related
chordate, which have documented conserved features such as neurons within the heart (intrinsic neurons).
Unlike mammalian hearts that cease proliferating shortly after birth, Ciona hearts proliferate during development
and into adulthood. The neurons associated with Ciona hearts are peptidergic, suggesting neuropeptides are
secreted from these neurons. Tachykinin is a conserved family of neuropeptides that includes Substance P,
which is implicated in cardiac disease, and is secreted from nerves that innervate the heart in vertebrates. The
function of neural innervation in Ciona is not known, however we have preliminary data indicating the
neuropeptide tachykinin promotes cardiac proliferation in the developing and adult Ciona heart. The sole article
documenting Ciona heart innervation has not been followed up, and thus we investigated if there was
unappreciated extrinsic innervation that exists in Ciona hearts. We find evidence of neurons from the brain
(extrinsic) of Ciona innervating the intrinsic neurons of the heart. We hypothesize that neuronal input promotes
proliferation in developing Ciona hearts. This hypothesis is supported by our preliminary data that the developing
Ciona heart is innervated by extrinsic and intrinsic neurons. Furthermore, our data suggest tachykinin signaling
promotes cardiac proliferation in developing and adult animals. Last, our preliminary single cell RNA-seq data
suggest intrinsic neurons in the heart can respond to tachykinin. We propose the following aims to investigate
our hypothesis.
Aim I: Characterize neuronal innervation of the Ciona heart. We will determine the temporal and spatial time-
course of neural innervation of the Ciona heart. We will use single cell RNA-seq to identify markers of all cell
types in the heart including those expressing the tachykinin receptor (neurokinin) and subtypes of neurons.
Aim II: Determine whether neuronal signaling regulates cardiac cell proliferation. We will identify the
developmental time-point(s) which tachykinin activates cardiomyocyte proliferation. Next we will prevent
tachykinin signaling in intrinsic neurons or cardiomyocytes to determine what cell type tachykinin acts on. We
will investigate if tachykinin promotes cardiomyocyte proliferation indirectly by testing if the growth factors
released by intrinsic neurons promote cardiomyocyte proliferation directly. My ultimate career goal is to study
the...

## Key facts

- **NIH application ID:** 10917108
- **Project number:** 5F32HL170997-02
- **Recipient organization:** SWARTHMORE COLLEGE
- **Principal Investigator:** Hannah Gruner
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $78,012
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917108

## Citation

> US National Institutes of Health, RePORTER application 10917108, Revealing the mechanisms of neural-mediated cardiac proliferation in Ciona robusta (5F32HL170997-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10917108. Licensed CC0.

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