RT Journal Article
SR Electronic
T1 <em>Myc</em> is dispensable for cardiac development in the mouse but rescues <em>Mycn</em>-deficient hearts through functional replacement and cell competition
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 357335
DO 10.1101/357335
A1 Muñoz-Martín, Noelia
A1 Sierra, Rocío
A1 Schimmang, Thomas
A1 Campo, Cristina Villa del
A1 Torres, Miguel
YR 2018
UL http://biorxiv.org/content/early/2018/08/08/357335.abstract
AB 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 Myc floxed allele with the Nkx2.5Cre 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 Mycn is essential for cardiomyocyte proliferation and cardiogenesis. Mosaic Myc overexpression in a Mycn-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 Myc is dispensable during cardiogenesis and adult heart homeostasis and Mycn is exclusively responsible for cardiomyocyte proliferation during heart development. Nonetheless, our results show that Myc can functionally replace Mycn. We also show that cardiomyocytes compete according to their overall Myc+Mycn levels and that Cell Competition eliminates flawed cardiomyocytes, suggesting its relevance as a quality control mechanism in cardiac development.