Nppa and Nppb act redundantly during zebrafish cardiac development to confine AVC marker expression and reduce cardiac jelly volume

Development
Daniela R GrassiniKelly A Smith

Abstract

Atrial natriuretic peptide (nppa/anf) and brain natriuretic peptide (nppb/bnp) form a gene cluster with expression in the chambers of the developing heart. Despite restricted expression, a function in cardiac development has not been demonstrated by mutant analysis. This is attributed to functional redundancy; however, their genomic location in cis has impeded formal analysis. Using genome editing, we have generated mutants for nppa and nppb, and found that single mutants were indistinguishable from wild type, whereas nppa/nppb double mutants displayed heart morphogenesis defects and pericardial oedema. Analysis of atrioventricular canal (AVC) markers show expansion of bmp4, tbx2b, has2 and versican expression into the atrium of double mutants. This expanded expression correlates with increased extracellular matrix in the atrium. Using a biosensor for hyaluronic acid to measure the cardiac jelly (cardiac extracellular matrix), we confirmed cardiac jelly expansion in nppa/nppb double mutants. Finally, bmp4 knockdown rescued the expansion of has2 expression and cardiac jelly in double mutants. This definitively shows that nppa and nppb function redundantly during cardiac development to restrict gene expression to the AVC, prevent...Continue Reading

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Citations

Feb 26, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Daniela R GrassiniKelly A Smith
Feb 20, 2020·Circulation Research·Felix GunawanAnabela Bensimon-Brito
Aug 9, 2020·Thyroid : Official Journal of the American Thyroid Association·Cho Rong HanSheue-Yann Cheng
Aug 15, 2020·Frontiers in Physiology·Kazuhide S Okuda, Benjamin M Hogan
Oct 28, 2020·Circulation Research·Joyce C K ManVincent M Christoffels
Feb 8, 2021·Environmental Pollution·Jinze MaHuiqiang Lu
Mar 7, 2021·Development·Christopher J Derrick, Emily S Noël
May 16, 2021·The Science of the Total Environment·Xin Chen, Wenhua Li
Jul 9, 2020·Chemical Research in Toxicology·Roman LiJulia Hoeng

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