Genetics & development of cardiac defects
Team Leader
S. ZAFFRAN
S. ZAFFRAN
Our work over the past few years has established the role of retinoic acid in defining the boundary of the heart fields during early development. Inhibition of retinoic acid signaling leads to expansion of cardiac progenitors. We have also shown that anterior Hox genes, as downstream targets of retinoic acid, are expressed in distinct domains of the second heart field contributing to the outflow tract and atria. Using mutant mouse embryos, we have recently demonstrated that Hoxb1 regulates proliferation and differentiation of second heart field progenitors and genetically interacts with Hoxa1 during cardiac outflow tract development. The role of retinoic acid signal and Hox genes in the patterning of the second heart field is being investigated.
Finally, elucidating the mechanisms involved in the restriction of cardiac progenitors will lead to a better understanding of CHDs and will ultimately lead to the development of novel therapies aimed at healing impaired human hearts.
Anomalies of heart valves, including bicuspid aortic valve (BAV), are some of the commonest CHDs. Extracellular matrix changes occur in many valvular diseases. However, the molecular mechanisms leading to these pathologies are poorly understood. We have recently discovered the role of the zinc finger transcription factor Krox20 (Egr2) during heart valve development in mice. Loss of Krox20 function leads to defective aortic valve structure associated with aortic dysfunction. Functional promoter analysis demonstrated that Krox20 regulates the fibrilar collagens Col1a1 and Col3a1 genes during the remodeling of aortic valves. We continue our studies to uncover the contribution of different lineages in valve development and disease. We are now using state-of-the-art genetic technologies including next generation whole exome sequencing with the goal of discovering new genes in aortic valve disease such as BAV.
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Telephone: 04 91 32 49 36
IR Ph.D.
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Telephone: 04 91 32 41 55
PUPH
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Telephone: 04 91 38 63 77
PH MD
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Telephone: 0491388120
IE
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POST-DOC
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DOCTORANT(E)
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AI
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Telephone: 0491324155
POST-DOC
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PUPH
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DOCTORANT(E)
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IE
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DR1 (PhD., HDR)
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Telephone: 04 91 32 49 36