2024-03-29T10:59:15Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/132522022-11-02T10:52:41Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
Repisalud
author
Munoz Martin, Noelia
author
Sierra, Rocio
author
Schimmang, Thomas
author
Villa del Campo, Cristina
author
Torres, Miguel
funder
Fondation Leducq
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Instituto de Salud Carlos III
funder
Fundación La Caixa
funder
Fundación ProCNIC
2021-07-22T10:27:37Z
2021-07-22T10:27:37Z
2019-02-01
Development. 2019; 146(3):170753
0950-1991
http://hdl.handle.net/20.500.12105/13252
30642836
10.1242/dev.170753
1477-9129
Development (Cambridge, England)
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 in cardiomyocytes both during cardiogenesis and for adult heart homeostasis, and that 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 combined Myc and Mycn levels and that cell competition eliminates flawed cardiomyocytes, suggesting its relevance as a quality control mechanism in cardiac development.
eng
Myc is dispensable for cardiomyocyte development but rescues Mycn-deficient hearts through functional replacement and cell competition.
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/13252/1/MycIsDispensableFor_2019.pdf
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MycIsDispensableFor_2019.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/13252/3/MycIsDispensableFor_2019.pdf.txt
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MycIsDispensableFor_2019.pdf.txt