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首页> 外文期刊>Development >Nppa and Nppb act redundantly during zebrafish cardiac development to confine AVC marker expression and reduce cardiac jelly volume.
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Nppa and Nppb act redundantly during zebrafish cardiac development to confine AVC marker expression and reduce cardiac jelly volume.

机译:在斑马鱼心脏开发期间,NPPA和NPPB冗余行为将AVC标记表达限制并减少心脏果冻体积。

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摘要

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, preventing excessive cardiac jelly synthesis in the atrial chamber.
机译:NPPA / ANF)和脑利钠肽(NPPB / BNP)形成基因簇,其表达在显影心脏的腔室中。尽管表达有限,但突变分析尚未证明心脏发育的功能。这归因于功能冗余;然而,他们在CIS中的基因组定位受到了正式的分析。使用基因组编辑,我们为NPPA和NPPB产生了突变体,发现单个突变体与野生型难以区分,而NPPA / NPPB双突变体显示心脏形态发生缺陷和心包水肿。地室管道(AVC)标记分析显示BMP4,TBX2B,HAS2和VERSICAN表达到双突变体中的膨胀。这种扩展的表达与庭在中胞内的增加的细胞外基质相关。使用生物传感器用于透明质酸测量心脏果冻(心肌细胞外基质),我们确认了NPPA / NPPB双突变体中的心脏果冻膨胀。最后,BMP4敲低救出了双突变体中HAS2表达和心脏果冻的扩张。这绝对地显示NPPA和NPPB在心脏发育过程中冗余的功能,以限制对AVC的基因表达,防止心房室中的过度心脏果冻合成。

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