Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate
- Hubrecht Institute, Netherlands
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
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Spatially resolved RNA-sequencing of the embryonic zebrafish heartPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE104057).
Article and author information
Author details
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
© 2018, Burkhard & Bakkers
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.
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Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate
eLife 7:e31515.
https://doi.org/10.7554/eLife.31515
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