Kemmler Cassie L, Riemslagh Fréderike W, Moran Hannah R, Mosimann Christian
Department of Pediatrics, Section of Developmental Biology, University of Colorado School of Medicine and Children's Hospital Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
J Cardiovasc Dev Dis. 2021 Feb 10;8(2):17. doi: 10.3390/jcdd8020017.
The heart is the first functional organ to form during vertebrate development. Congenital heart defects are the most common type of human birth defect, many originating as anomalies in early heart development. The zebrafish model provides an accessible vertebrate system to study early heart morphogenesis and to gain new insights into the mechanisms of congenital disease. Although composed of only two chambers compared with the four-chambered mammalian heart, the zebrafish heart integrates the core processes and cellular lineages central to cardiac development across vertebrates. The rapid, translucent development of zebrafish is amenable to in vivo imaging and genetic lineage tracing techniques, providing versatile tools to study heart field migration and myocardial progenitor addition and differentiation. Combining transgenic reporters with rapid genome engineering via CRISPR-Cas9 allows for functional testing of candidate genes associated with congenital heart defects and the discovery of molecular causes leading to observed phenotypes. Here, we summarize key insights gained through zebrafish studies into the early patterning of uncommitted lateral plate mesoderm into cardiac progenitors and their regulation. We review the central genetic mechanisms, available tools, and approaches for modeling congenital heart anomalies in the zebrafish as a representative vertebrate model.
心脏是脊椎动物发育过程中形成的首个功能器官。先天性心脏缺陷是人类最常见的出生缺陷类型，许多都源于早期心脏发育异常。斑马鱼模型为研究早期心脏形态发生以及深入了解先天性疾病机制提供了一个易于研究的脊椎动物系统。尽管与具有四个腔室的哺乳动物心脏相比，斑马鱼心脏仅由两个腔室组成，但它整合了整个脊椎动物心脏发育核心过程和细胞谱系。斑马鱼快速、透明的发育过程适合进行体内成像和遗传谱系追踪技术，为研究心脏场迁移、心肌祖细胞添加和分化提供了多种工具。通过CRISPR-Cas9将转基因报告基因与快速基因组工程相结合，能够对与先天性心脏缺陷相关的候选基因进行功能测试，并发现导致观察到的表型的分子原因。在这里，我们总结了通过斑马鱼研究在未分化的侧板中胚层向心脏祖细胞的早期模式形成及其调控方面所获得的关键见解。我们回顾了作为代表性脊椎动物模型的斑马鱼中先天性心脏异常建模的核心遗传机制、可用工具和方法。
