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Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region

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Title: Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region
Authors: Abu Nahia, K
Migdal, M
Quinn, TA
Poon, K-L
Lapinski, M
Sulej, A
Liu, J
Mondal, SS
Pawlak, M
Bugajski, L
Piwocka, K
Brand, T
Kohl, P
Korzh, V
Winata, C
Item Type: Journal Article
Abstract: The atrioventricular canal (AVC) is the site where key structures responsible for functional division between heart regions are established, most importantly, the atrioventricular (AV) conduction system and cardiac valves. To elucidate the mechanism underlying AVC development and function, we utilized transgenic zebrafish line sqet31Et expressing EGFP in the AVC to isolate this cell population and profile its transcriptome at 48 and 72 hpf. The zebrafish AVC transcriptome exhibits hallmarks of mammalian AV node, including the expression of genes implicated in its development and those encoding connexins forming low conductance gap junctions. Transcriptome analysis uncovered protein-coding and noncoding transcripts enriched in AVC, which have not been previously associated with this structure, as well as dynamic expression of epithelial-to-mesenchymal transition markers and components of TGF-β, Notch, and Wnt signaling pathways likely reflecting ongoing AVC and valve development. Using transgenic line Tg(myl7:mermaid) encoding voltage-sensitive fluorescent protein, we show that abolishing the pacemaker-containing sinoatrial ring (SAR) through Isl1 loss of function resulted in spontaneous activation in the AVC region, suggesting that it possesses inherent automaticity although insufficient to replace the SAR. The SAR and AVC transcriptomes express partially overlapping species of ion channels and gap junction proteins, reflecting their distinct roles. Besides identifying conserved aspects between zebrafish and mammalian conduction systems, our results established molecular hallmarks of the developing AVC which underlies its role in structural and electrophysiological separation between heart chambers. This data constitutes a valuable resource for studying AVC development and function, and identification of novel candidate genes implicated in these processes.
Issue Date: 23-Sep-2021
Date of Acceptance: 10-Sep-2021
URI: http://hdl.handle.net/10044/1/92205
DOI: 10.1007/s00018-021-03939-y
ISSN: 1420-682X
Publisher: Springer
Start Page: 6669
End Page: 6687
Journal / Book Title: Cellular and Molecular Life Sciences
Volume: 78
Copyright Statement: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Atrioventricular canal
Atrioventricular node
Cardiac valve
Cardiac pacemaker
Zebrafish
RNA-seq
EPITHELIAL-MESENCHYMAL TRANSITION
CARDIAC CONDUCTION
IN-VIVO
IMPULSE PROPAGATION
ENHANCER TRAP
PROTEIN ISL-1
OUTFLOW TRACT
HEART
DIFFERENTIATION
JUNCTION
Atrioventricular canal
Atrioventricular node
Cardiac pacemaker
Cardiac valve
RNA-seq
Zebrafish
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Atrioventricular canal
Atrioventricular node
Cardiac valve
Cardiac pacemaker
Zebrafish
RNA-seq
EPITHELIAL-MESENCHYMAL TRANSITION
CARDIAC CONDUCTION
IN-VIVO
IMPULSE PROPAGATION
ENHANCER TRAP
PROTEIN ISL-1
OUTFLOW TRACT
HEART
DIFFERENTIATION
JUNCTION
Biochemistry & Molecular Biology
0601 Biochemistry and Cell Biology
0606 Physiology
1103 Clinical Sciences
Publication Status: Published
Online Publication Date: 2021-09-23
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons