Cardiovascular development is a complex achievement that requires interaction of multiple cells types during a tightly orchestrated time frame. Cell commitment and interplay are tightly regulated by a vast number of transcription factors during cardiogenesis. Over the last decade we have learned key and pivotal roles of distinct cardiac-enriched transcription factors and within this session four excellent speakers highlighted their distinct roles in cardiac conduction system formation, vascular remodelling, myocardial architecture and epicardial contribution to the developing and adult heart.
New understanding of cardiovascular development
Vincent Christoffels (Amsterdam) reported seminal work on the transcriptional role of a Tbox family member, Tbx3, regulating gene activation and function of distinct components of the developing cardiac conduction system. Using different genetic approaches, Dr Christoffels demonstrated that this transcription factor is crucial to regulate the gene expression boundaries of the sinoatrial node, atrioventricular node and proximal part of the fast ventricular conduction system.
On a different topic, but tightly related to cardiovascular development, Dr. Buschmann (Berlin) reported the importance of shear-stress on the onset of gene expression of distinct early responsive players such as eNOS and ICAM-1 during the process of collateral arteries remodelling, a process dubbed arteriogenesis.
Marina Campione (Padova, IT) reported the role of the homebox transcription factor Pitx2 during cardiac development by illustrating the phenotypical dysmorphogenesis of conditional transgenic mice that selectively lack expression of Pitx2 in the myocardial tissue during cardiogenesis. Pitx2, a key regulator of left-right asymmetry during gastrulation, seems to play pivotal roles in modulating cell shape organization in a heterogeneous manner during ventricular chamber development. Interestingly, such a phenomenon might be considered reminiscent of its early regionalized expression pattern during heart formation.
Finally, Jose Maria Perez-Pomares (Malaga) reported on the role of Will’s tumor transcription factor (Wt1) during the formation and cardiovascular contribution of the epicardial layer. A set of distinct in vivo and in vitro experimental approaches demonstrate that Wt1 plays key roles during epicardial formation as well as during its subsequent migration and colonization of the developing heart. Furthermore, a direct link between Wt1 role and retinoic acid signalling in the developing cardiovascular system was highly supported.