Cxcr4a regulates heart progenitor development and cardiac rhythm in zebrafish

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry and Biophysics Reports Pub Date : 2024-07-13 DOI:10.1016/j.bbrep.2024.101782
Bingyu Chen , Qin Ran , Xin Chen , Zhilin Deng , Rong Zhou , Yu Zhang , Min Liu , Botong Li , Shuying Huang , Peijian Wang , Sizhou Huang
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Abstract

Cxcr4a is involved in multiple organ development including coronary vasculature formation and heart left-right (LR) patterning, whether it is involved in heart progenitor determination and cardiac rhythm regulation is not addressed. Here we showed that in cxcr4a mutants, from 2 days post fertilization (dpf) to 4dpf the embryos transiently displayed pericardial edema and increased cardiac rhythm. While from 5dpf, the heart phenotype disappeared. Detailed analysis demonstrated that, at 36hpf and 48hpf, even though there was no distinct difference in the heart size between cxcr4a mutants and controls, the expression of myl7 was decreased. Further data showed that, the heart progenitors were decreased at 18SS(Somite Stage). Mechanically, RNA-seq, RT-qPCR and in situ experiments showed that the retinoic acid (RA) signaling was upregulated, and the up-regulation of RA signaling may mediate the role of cxcr4a in regulating heart progenitor development. In addition, we also identified that low dose of RA treatment accelerated the cardiac rhythm, being similar to that in cxcr4a mutants. Decreasing RA signaling partially restored the rapid cardiac rhythm in cxcr4a mutants, implying the possibility that RA signaling partially mediates the role of cxcr4a in regulating cardiac rhythm. In conclusion, our study identified cxcr4a simultaneously regulates heart progenitor determination and cardiac rhythm.

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Cxcr4a调控斑马鱼心脏祖细胞的发育和心律
Cxcr4a 参与了多个器官的发育,包括冠状血管的形成和心脏左右(LR)模式的形成,但它是否参与了心脏祖细胞的确定和心律的调节尚未解决。在这里,我们发现在 cxcr4a 突变体中,从受精后 2 天(dpf)到 4dpf 胚胎会短暂出现心包水肿和心律增快。而从 5dpf 开始,心脏表型消失。详细分析显示,在36hpf和48hpf时,尽管cxcr4a突变体和对照组的心脏大小没有明显差异,但myl7的表达却下降了。进一步的数据显示,在18SS(体细胞期),心脏祖细胞减少。RNA-seq、RT-qPCR和原位实验表明,视黄酸(RA)信号被上调,RA信号的上调可能介导了cxcr4a在心脏祖细胞发育中的调控作用。此外,我们还发现低剂量的RA处理会加速心脏节律,这与cxcr4a突变体的情况相似。减少 RA 信号传导可部分恢复 cxcr4a 突变体的快速心律,这意味着 RA 信号传导可能部分介导了 cxcr4a 在调节心律中的作用。总之,我们的研究发现cxcr4a同时调控心脏祖细胞的确定和心律。
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来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
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