Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate

Abstract
Data availability
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Abstract

Development of specialized cells and structures in the heart is regulated by spatially-restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially-restricted molecular pathways critical for specific cardiac functions.

Data availability

The following data sets were generated

1. Burkhard SB
2. Bakkers J
(2017) Spatially resolved RNA-sequencing of the embryonic zebrafish heart
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE104057).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE104057

Article and author information

Author details

Silja Barbara Burkhard

Cardiac Development and Genetics, Hubrecht Institute, Utrecht, Netherlands

Competing interests
The authors declare that no competing interests exist.
Jeroen Bakkers

Cardiac Development and Genetics, Hubrecht Institute, Utrecht, Netherlands

For correspondence
j.bakkers@hubrecht.eu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9418-0422

Funding

ZonMw (91212086)

Silja Barbara Burkhard

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (022.001.003)

Silja Barbara Burkhard

CVON - Netherlands Heart Foundation (CVON-CONCORgenes)

Silja Barbara Burkhard

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All studies involving vertebrate animals were performed with institutional approval in compliance with institutional ethical guidelines. (KNAW DEC 14-01)

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.