Imperial College London
Alternate

ProfessorThomasBrand

Faculty of Medicine, National Heart & Lung Institute

Chair in Developmental Dynamics
 
 
 
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Contact

 

+44 (0)20 7594 8744t.brand Website CV

 
 
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Assistant

 

Miss Cheryl Costello +44 (0)20 7594 3001

 
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Location

 

433ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Abu:2021:10.1007/s00018-021-03939-y,
author = {Abu, Nahia K and Migdal, M and Quinn, TA and Poon, K-L and Lapinski, M and Sulej, A and Liu, J and Mondal, SS and Pawlak, M and Bugajski, L and Piwocka, K and Brand, T and Kohl, P and Korzh, V and Winata, C},
doi = {10.1007/s00018-021-03939-y},
journal = {Cellular and Molecular Life Sciences},
pages = {6669--6687},
title = {Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region},
url = {http://dx.doi.org/10.1007/s00018-021-03939-y},
volume = {78},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Abu,Nahia K
AU  - Migdal,M
AU  - Quinn,TA
AU  - Poon,K-L
AU  - Lapinski,M
AU  - Sulej,A
AU  - Liu,J
AU  - Mondal,SS
AU  - Pawlak,M
AU  - Bugajski,L
AU  - Piwocka,K
AU  - Brand,T
AU  - Kohl,P
AU  - Korzh,V
AU  - Winata,C
DO  - 10.1007/s00018-021-03939-y
EP  - 6687
PY  - 2021///
SN  - 1420-682X
SP  - 6669
TI  - Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region
T2  - Cellular and Molecular Life Sciences
UR  - http://dx.doi.org/10.1007/s00018-021-03939-y
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000698570100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://link.springer.com/article/10.1007%2Fs00018-021-03939-y
UR  - http://hdl.handle.net/10044/1/92205
VL  - 78
ER  -
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