Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/?-catenin signaling in autonomic control of heart rate.
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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/?-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/?-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.
SUBMITTER: Burkhard SB
PROVIDER: S-EPMC5815850 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
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