Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration
Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration
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DOI：
10.1242/dev.106336
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发表时间：
2014-08-01
期刊：
影响因子：
4.6
通讯作者：
Yelon, Deborah
中科院分区：
文献类型：
--
作者：
Schindler, Yocheved L.;Garske, Kristina M.;Yelon, Deborah
胚胎心脏的形成需要产生适当数量的心肌细胞;同样，损伤后的心脏再生依赖于丢失的心肌细胞的恢复。碱性螺旋-环-螺旋（bHLH）转录因子Hand 2参与促进心肌细胞形成。然而，目前还不清楚Hand 2在这一过程中是否发挥了指导性或许可性的作用。在这里，我们发现在早期斑马鱼胚胎中hand 2的过度表达能够增强心肌细胞的产生，导致心脏扩大，流出道的大小显著增加。我们的证据表明，这些增加是依赖于Hand 2在多聚体复合物中的相互作用，并独立于Hand 2的直接DNA结合。增殖实验表明，hand 2可以通过促进第二心脏区域内的晚期分化的心脏祖细胞的分裂来影响心肌细胞的产生。此外，我们的数据表明，手2可以影响心肌细胞的生产，通过改变前侧板中胚层的图案，可能有利于形成的第一心脏领域的造血和血管谱系的代价。hand 2在胚胎心脏发生过程中的效力表明，hand 2也可以影响成年斑马鱼的心脏再生;事实上，我们发现hand 2的过表达可以增强心肌细胞对损伤的再生增殖。总之，我们的研究表明，hand 2可以在多种情况下通过多种机制驱动心肌细胞的产生。这些结果有助于我们了解先天性心脏病的潜在起源，并为再生医学的未来策略提供信息。
Embryonic heart formation requires the production of an appropriate number of cardiomyocytes; likewise, cardiac regeneration following injury relies upon the recovery of lost cardiomyocytes. The basic helix-loop-helix (bHLH) transcription factor Hand2 has been implicated in promoting cardiomyocyte formation. It is unclear, however, whether Hand2 plays an instructive or permissive role during this process. Here, we find that overexpression of hand2 in the early zebrafish embryo is able to enhance cardiomyocyte production, resulting in an enlarged heart with a striking increase in the size of the outflow tract. Our evidence indicates that these increases are dependent on the interactions of Hand2 in multimeric complexes and are independent of direct DNA binding by Hand2. Proliferation assays reveal that hand2 can impact cardiomyocyte production by promoting division of late-differentiating cardiac progenitors within the second heart field. Additionally, our data suggest that hand2 can influence cardiomyocyte production by altering the patterning of the anterior lateral plate mesoderm, potentially favoring formation of the first heart field at the expense of hematopoietic and vascular lineages. The potency of hand2 during embryonic cardiogenesis suggested that hand2 could also impact cardiac regeneration in adult zebrafish; indeed, we find that overexpression of hand2 can augment the regenerative proliferation of cardiomyocytes in response to injury. Together, our studies demonstrate that hand2 can drive cardiomyocyte production in multiple contexts and through multiple mechanisms. These results contribute to our understanding of the potential origins of congenital heart disease and inform future strategies in regenerative medicine.