Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and nkx2.5 function
Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and nkx2.5 function
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DOI：
10.1242/dev.088351
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发表时间：
2013-03-01
期刊：
影响因子：
4.6
通讯作者：
Burns, C. Geoffrey
中科院分区：
文献类型：
--
作者：
Guner-Ataman, Burcu;Paffett-Lugassy, Noelle;Burns, C. Geoffrey
第二心野（SHF）祖细胞在哺乳动物心脏发生过程中发挥重要作用。我们最近在斑马鱼中发现了一群表达潜伏TGF β结合蛋白3 （ltbp3）的心脏祖细胞（CPCs），这些细胞表现出哺乳动物前路SHF的几个决定性特征。然而，ltbp3转录本在高等脊椎动物中指定的SHF祖细胞——前外侧板中胚层（ALPM）中明显缺失。相反，ltbp3的表达始于发育中的心管的动脉极。由于心脏发育的机制在进化上是保守的，我们假设斑马鱼的SHF规范也发生在ALPM中。为了验证这一假设，我们基于ALPM模式的进化保守性，对预测含有SHF祖细胞的gata4（+）和nkx2.5(+) ALPM群体进行了Cre/loxP谱系追踪。在shf衍生的远端心室心肌和流出道（OFT）的三个谱系中发现了追踪的细胞。我们用Kaede光转化证实了ALPM nkx2.5+细胞的贡献程度。综上所述，这些数据表明，与高等脊椎动物一样，斑马鱼的SHF祖细胞在ALPM中被指定并表达nkx2.5。此外，我们验证了Nkx2.5在斑马鱼SHF发育过程中起保守和重要作用的假设。注射nkx2.5 morpholino的胚胎表现出由祖细胞增殖受损引起的SHF表型。同时注射低剂量的nkx2.5和ltbp3 morpholinos揭示了这些因素之间的遗传相互作用。总之，我们的数据突出了斑马鱼SHF发育的两个保守特征，揭示了nkx2.5和ltbp3之间的一种新的遗传关系，并强调了这种模式生物在破译SHF生物学方面的实用性。
Second heart field (SHF) progenitors perform essential functions during mammalian cardiogenesis. We recently identified a population of cardiac progenitor cells (CPCs) in zebrafish expressing latent TGF beta-binding protein 3 (ltbp3) that exhibits several defining characteristics of the anterior SHF in mammals. However, ltbp3 transcripts are conspicuously absent in anterior lateral plate mesoderm (ALPM), where SHF progenitors are specified in higher vertebrates. Instead, ltbp3 expression initiates at the arterial pole of the developing heart tube. Because the mechanisms of cardiac development are conserved evolutionarily, we hypothesized that zebrafish SHF specification also occurs in the ALPM. To test this hypothesis, we Cre/loxP lineage traced gata4(+) and nkx2.5(+) ALPM populations predicted to contain SHF progenitors, based on evolutionary conservation of ALPM patterning. Traced cells were identified in SHF-derived distal ventricular myocardium and in three lineages in the outflow tract (OFT). We confirmed the extent of contributions made by ALPM nkx2.5+ cells using Kaede photoconversion. Taken together, these data demonstrate that, as in higher vertebrates, zebrafish SHF progenitors are specified within the ALPM and express nkx2.5. Furthermore, we tested the hypothesis that Nkx2.5 plays a conserved and essential role during zebrafish SHF development. Embryos injected with an nkx2.5 morpholino exhibited SHF phenotypes caused by compromised progenitor cell proliferation. Co-injecting low doses of nkx2.5 and ltbp3 morpholinos revealed a genetic interaction between these factors. Taken together, our data highlight two conserved features of zebrafish SHF development, reveal a novel genetic relationship between nkx2.5 and ltbp3, and underscore the utility of this model organism for deciphering SHF biology.