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The Molecular Mechanisms of Heart Regeneration

Adult zebrafish are capable of completely regenerating their heart after an extensive insult. Previously, we determined that the regenerated myocardium was produced by the proliferation of existing cardiomyocytes and not, as had p... ver más

28/02/2017

CNRS

100K€

Presupuesto del proyecto: 100K€

Líder del proyecto

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2017-02-28 No tenemos la información de la convocatoria

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Líder del proyecto

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 100K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Adult zebrafish are capable of completely regenerating their heart after an extensive insult. Previously, we determined that the regenerated myocardium was produced by the proliferation of existing cardiomyocytes and not, as had previously been reported, by stem/progenitor cells. Analysis of regenerating hearts shows that soon after injury cardiomyocytes detach from one another and dedifferentiate, disassembling their sarcomeric structure in the process. In situ and microarray analysis indicate that dynamic changes in gene expression are also associated with heart regeneration. At present only handful of genes have been directly linked to heart regeneration in zebrafish. Our main objective is to expand this small list and thus provide candidates which can subsequently be manipulated in mammals. To determine suitable target genes, we will make use of the substantial microarray data generated from studying heart regeneration in zebrafish. Importantly, this data has revealed that certain genes shown to be up-regulated during zebrafish heart regeneration have previously been shown to positively regulate cardiomyocyte proliferation in mammalian models. These findings not only indicate that zebrafish and mammals share similar genetic mechanisms as far as regulating cardiomyocyte proliferation but also verify that the data represented in the microarrays contains positive candidate genes. Once candidates have been selected and confirmed in our zebrafish model system, we will begin testing these in vitro in mammalian cardiomyocytes before creating transgenic mouse models to determine whether they are capable of inducing myocardial regeneration following cardiac ischemia.

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