@article {120,
	title = {Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region.},
	journal = {Cell Mol Life Sci},
	volume = {78},
	year = {2021},
	month = {2021 Oct},
	pages = {6669-6687},
	abstract = {<p>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.</p>},
	keywords = {Animals, Animals, Genetically Modified, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Genome, Genomics, Heart Septal Defects, Heart Valves, Myocardium, Organogenesis, Pacemaker, Artificial, Wnt Signaling Pathway, Zebrafish, Zebrafish Proteins},
	issn = {1420-9071},
	doi = {10.1007/s00018-021-03939-y},
	author = {Abu Nahia, Karim and Migda{\l}, Maciej and Quinn, T Alexander and Poon, Kar-Lai and {\L}api{\'n}ski, Maciej and Sulej, Agata and Liu, Jiandong and Mondal, Shamba S and Pawlak, Micha{\l} and Bugajski, {\L}ukasz and Piwocka, Katarzyna and Brand, Thomas and Kohl, Peter and Korzh, Vladimir and Winata, Cecilia}
}
@article {112,
	title = {Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development.},
	journal = {Genome Res},
	volume = {29},
	year = {2019},
	month = {2019 03},
	pages = {506-519},
	abstract = {<p>Organogenesis involves dynamic regulation of gene transcription and complex multipathway interactions. Despite our knowledge of key factors regulating various steps of heart morphogenesis, considerable challenges in understanding its mechanism still exist because little is known about their downstream targets and interactive regulatory network. To better understand transcriptional regulatory mechanism driving heart development and the consequences of its disruption in vivo, we performed time-series analyses of the transcriptome and genome-wide chromatin accessibility in isolated cardiomyocytes (CMs) from wild-type zebrafish embryos at developmental stages corresponding to heart tube morphogenesis, looping, and maturation. We identified genetic regulatory modules driving crucial events of heart development that contained key cardiac TFs and are associated with open chromatin regions enriched for DNA sequence motifs belonging to the family of the corresponding TFs. Loss of function of cardiac TFs Gata5, Tbx5a, and Hand2 affected the cardiac regulatory networks and caused global changes in chromatin accessibility profile, indicating their role in heart development. Among regions with differential chromatin accessibility in mutants were highly conserved noncoding elements that represent putative enhancers driving heart development. The most prominent gene expression changes, which correlated with chromatin accessibility modifications within their proximal promoter regions, occurred between heart tube morphogenesis and looping, and were associated with metabolic shift and hematopoietic/cardiac fate switch during CM maturation. Our results revealed the dynamic regulatory landscape throughout heart development and identified interactive molecular networks driving key events of heart morphogenesis.</p>},
	keywords = {Animals, Cells, Cultured, Chromatin, Chromatin Assembly and Disassembly, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Heart, Myocytes, Cardiac, Transcription Factors, Transcriptome, Zebrafish, Zebrafish Proteins},
	issn = {1549-5469},
	doi = {10.1101/gr.244491.118},
	author = {Pawlak, Michal and Kedzierska, Katarzyna Z and Migdal, Maciej and Nahia, Karim Abu and Ramilowski, Jordan A and Bugajski, Lukasz and Hashimoto, Kosuke and Marconi, Aleksandra and Piwocka, Katarzyna and Carninci, Piero and Winata, Cecilia L}
}
