TY - JOUR
T1 - Twisting of the zebrafish heart tube during cardiac looping is a tbx5-dependent and tissue-intrinsic process
AU - Tessadori, Federico
AU - Tsingos, Erika
AU - Colizzi, Enrico Sandro
AU - Kruse, Fabian
AU - Van Den Brink, Susanne C.
AU - Van Den Boogaard, Malou
AU - Christoffels, Vincent M.
AU - Merks, Roeland M.H.
AU - Bakkers, Jeroen
N1 - Funding Information:
The authors thank Anko de Graaff (Hubrecht Imaging Center) for assistance with microscopic imaging, Phong Nguyen (Hubrecht Institute) for carrying out the ISH cryosections and critically reading the manuscript and Hessel Honkoop (Hubrecht Institute) for critically reading the manuscript. Funding: The authors wish to acknowledge the support from the Dutch Heart Foundation grant CVON2014-18CONCOR-GENES to JB and VMC, support from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Nederlandse Wetenschapsagenda Startimpuls) to ESC and Neder-landse Organisatie voor Wetenschappelijk Onderzoek grant NWO/ENW-VICI 865.17.004 to RMHM.
Publisher Copyright:
© Tessadori et al.
PY - 2021/8
Y1 - 2021/8
N2 - Organ laterality refers to the left-right asymmetry in disposition and conformation of internal organs and is established during embryogenesis. The heart is the first organ to display visible left-right asymmetries through its left-sided positioning and rightward looping. Here, we present a new zebrafish loss-of-function allele for tbx5a, which displays defective rightward cardiac looping morphogenesis. By mapping individual cardiomyocyte behavior during cardiac looping, we establish that ventricular and atrial cardiomyocytes rearrange in distinct directions. As a consequence, the cardiac chambers twist around the atrioventricular canal resulting in torsion of the heart tube, which is compromised in tbx5a mutants. Pharmacological treatment and ex vivo culture establishes that the cardiac twisting depends on intrinsic mechanisms and is independent from cardiac growth. Furthermore, genetic experiments indicate that looping requires proper tissue patterning. We conclude that cardiac looping involves twisting of the chambers around the atrioventricular canal, which requires correct tissue patterning by Tbx5a.
AB - Organ laterality refers to the left-right asymmetry in disposition and conformation of internal organs and is established during embryogenesis. The heart is the first organ to display visible left-right asymmetries through its left-sided positioning and rightward looping. Here, we present a new zebrafish loss-of-function allele for tbx5a, which displays defective rightward cardiac looping morphogenesis. By mapping individual cardiomyocyte behavior during cardiac looping, we establish that ventricular and atrial cardiomyocytes rearrange in distinct directions. As a consequence, the cardiac chambers twist around the atrioventricular canal resulting in torsion of the heart tube, which is compromised in tbx5a mutants. Pharmacological treatment and ex vivo culture establishes that the cardiac twisting depends on intrinsic mechanisms and is independent from cardiac growth. Furthermore, genetic experiments indicate that looping requires proper tissue patterning. We conclude that cardiac looping involves twisting of the chambers around the atrioventricular canal, which requires correct tissue patterning by Tbx5a.
UR - http://www.scopus.com/inward/record.url?scp=85113892242&partnerID=8YFLogxK
U2 - 10.7554/eLife.61733
DO - 10.7554/eLife.61733
M3 - Article
C2 - 34372968
AN - SCOPUS:85113892242
SN - 2050-084X
VL - 10
SP - 1
EP - 34
JO - eLife
JF - eLife
M1 - e61733
ER -