Cardiovascular Development Program, Centro Nacional de Investigaciones Cardiovasculares, CNIC, 28029 Madrid, Spain.
Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, 47003, Valladolid, Spain.
Development. 2019 Feb 1;146(3):dev170753. doi: 10.1242/dev.170753.
Myc is considered an essential transcription factor for heart development, but cardiac defects have only been studied in global Myc loss-of-function models. Here, we eliminated Myc by recombining a floxed allele with the driver. We observed no anatomical, cellular or functional alterations in either fetuses or adult cardiac Myc-deficient mice. We re-examined Myc expression during development and found no expression in developing cardiomyocytes. In contrast, we confirmed that is essential for cardiomyocyte proliferation and cardiogenesis. Mosaic Myc overexpression in a -deficient background shows that Myc can replace Mycn function, recovering heart development. We further show that this recovery involves the elimination of Mycn-deficient cells by cell competition. Our results indicate that is dispensable in cardiomyocytes both during cardiogenesis and for adult heart homeostasis, and that is exclusively responsible for cardiomyocyte proliferation during heart development. Nonetheless, our results show that can functionally replace We also show that cardiomyocytes compete according to their combined Myc and Mycn levels and that cell competition eliminates flawed cardiomyocytes, suggesting its relevance as a quality control mechanism in cardiac development.
Myc 被认为是心脏发育所必需的转录因子，但心脏缺陷仅在全局 Myc 功能丧失模型中进行了研究。在这里，我们通过与 驱动子重组 floxed 等位基因来消除 Myc。我们在胎儿或成年心脏 Myc 缺陷型小鼠中均未观察到解剖、细胞或功能改变。我们重新检查了发育过程中的 Myc 表达情况，发现发育中的心肌细胞中没有 Myc 的表达。相比之下，我们证实 对于心肌细胞增殖和心脏发生是必不可少的。在 - 缺陷背景下的嵌合 Myc 过表达表明 Myc 可以替代 Mycn 的功能，恢复心脏发育。我们进一步表明，这种恢复涉及通过细胞竞争消除 Mycn 缺陷细胞。我们的结果表明，在心脏发生和成年心脏稳态期间， 在心肌细胞中是可有可无的，并且 专门负责心脏发育过程中心肌细胞的增殖。尽管如此，我们的结果表明， 可以在功能上替代 我们还表明，心肌细胞根据其合并的 Myc 和 Mycn 水平进行竞争，并且细胞竞争消除了有缺陷的心肌细胞，这表明它作为心脏发育中质量控制机制的相关性。
