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dc.contributor.advisorTorres, Miguel 
dc.contributor.authorMunoz Martin, Noelia
dc.description.abstractThe 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.es_ES
dc.description.sponsorshipThis work was performed in Miguel Torres’ laboratory in the Cell and Developmental Biology Area at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) in Madrid. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This study was funded by grants RD12/0019/0005 and RD16/0011/0019 (TerCel, RETICS); S2010-BMD-2315 (Comunidad de Madrid); BFU2012-31086 (MINECO); BFU2015-71519 (MEIC) and ref. 17CVD04 (Leudcq Foundation Transatlantic Networks). Noelia Muñoz Martín was recipient of a fellowship from “La Caixa-Severo Ochoa 2014” and EMBO-Short Term 2018.es_ES
dc.titleThe Role of Meis Transcription Factors in Cardiomyocyteses_ES
dc.typeTesis doctorales_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)
dc.contributor.funderFundación ProCNIC
dc.contributor.funderLeducq Foundation
dc.contributor.funderFundación La Caixa
dc.contributor.funderEuropean Molecular Biology Organization (EMBO)
dc.contributor.funderComunidad de Madrid
dc.repisalud.orgCNICCNIC::Grupos de investigación::Control Genético del Desarrollo y Regeneración de Órganoses_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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