May 3, 2019

Noelia Muñoz Martin

10.00-10:15 Noelia Muñoz Martin

‘Transcription factors: Regulation of heart development’

The heart is the first functional organ during embryo development and essential for the organism during the whole life. Have you ever wonder about how it is formed? How is this important process control?

In our group, we are studying the complex regulation of heart formation in mammals, using mice as experimental model. We aim to understand the role of two transcription factors, Myc and Meis, in heart development and homeostasis.
It has been accepted for decades that Myc was controlling cardiomyocytes proliferation during development. However, we recently demonstrated that, unlike Mycn, Myc conditional deletion in the heart do not lead to any phenotype and this is due to the absent expression of Myc in developing cardiomyocytes. However, ectopic mosaic expression of Myc can functionally compensate for the loss of Mycn in the heart by cell competition mechanisms.

Meis is known to control different processes in embryogenesis like hematopoiesis, limb and eye formation. We have found Meis expression in the myocardium (WM) and cardiac conduction system (CCS). Conditional deletion of Meis in cardiomyocytes during development lead to perinatal death. Optical mapping technique allowed us to find slower conduction velocity throughout the developing ventricles. This is consistent with decreased Cx43 expression in the ventricles. Echocardiography studies suggested arrhythmias might be promoting the embryonic death at the moment of delivery. RNA-seq data showed that loss of Meis function leads to an increased expression of genes controlling CCS differentiation while genes important for WM maturation are downregulated.

All together, we are a little bit closer to the understanding of the regulatory network controlling the fascinating process of cardiac formation.