Person:
Munoz Martin, Noelia

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Noelia
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Munoz Martin
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CNIC
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    Myc is dispensable for cardiomyocyte development but rescues Mycn-deficient hearts through functional replacement and cell competition.
    (The Company of Biologists, 2019-02-01) Munoz Martin, Noelia; Sierra, Rocio; Schimmang, Thomas; Villa del Campo, Cristina; Torres, Miguel; Fondation Leducq; Ministerio de Ciencia, Innovación y Universidades (España); Instituto de Salud Carlos III; Fundación La Caixa; Fundación ProCNIC
    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.
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    The Role of Meis Transcription Factors in Cardiomyocytes
    (2019-07-26) Munoz Martin, Noelia; Torres, Miguel; Ministerio de Ciencia, Innovación y Universidades (España); Fundación ProCNIC; Fondation Leducq; Fundación La Caixa; European Molecular Biology Organization; Comunidad de Madrid (España)
    The heart is the pump that irrigates the body to satisfy the nutrient and oxygen demands essential for keeping the organism alive. Understanding how the heart is formed and how its homeostasis is maintained in adulthood, is of great interest and can provide new insights on the etiology of cardiovascular diseases. In this doctoral thesis we studied the role of Meis1 and Meis2 transcription factors as possible regulators of cardiac development and homeostasis. We developed two mouse models for the conditional simultaneous deletion of Meis1 and Meis2 in cardiomyocytes either during development or during adulthood. Analysis of Meis1 and Meis2 double deletion in the developing heart revealed cardiac malformations and perinatal death, together with impaired electrical impulse propagation through the ventricles. Adult mice with Meis1 and Meis2 loss of function in cardiomyocytes presented mild cardiac hypertrophy, polyploidization of mononucleated cardiomyocytes and impaired electrical impulse conduction through ventricular myocardium. The transcriptomic analysis of the mutants suggests that Meis1 and Meis2 transcription factors regulate calcium and sodium currents and GAP junction communication in developing and adult cardiomyocytes, which is in accordance with the electrical phenotypes observed. Moreover, the set of genes sensitive to Meis1 and Meis2 deletion shows significant coincidence with those altered in mouse models of arrhythmogenic right ventricular cardiomyopathy, suggesting a role for these transcription factors in the pathogenesis of this disease.