Transcriptional Control of Cardiac Development and Arrhythmias

Leader: Vincent Christoffels

Expertise

The research group of Vincent Christoffels has worked for 7 years on the transcriptional regulation of compartment specific gene expression in the developing heart, and more recently on the morphogenetic mechanisms of the formation of the conduction system and valves. The group has experience in genetic manipulation of the mouse, and in the analysis of mouse embryos, of (trans) gene expression and of heart phenotypes. The group has experience in the molecular analysis of transcriptional regulation. We developed a non-radioactive in situ hybridization method on sections that is superior to radioactive in situ methods in terms of sensitivity, preservation of histology and efficiency. Additionally, an automated 3D reconstruction method was developed for the reconstruction of expression patterns in the heart. The group has recently carried out genetic lineage analysis of the distinct heart tissues.

Current research

Research focuses on the molecular and cellular mechanisms of the formation of the chambers and the nodes of the conduction system. T-box factors, particularly Tbx2 and Tbx3, are key-players in the local differentiation of working myocardium and the formation of atrioventricular canal, outflow tract and the nodes of the conduction system. The group focuses on the mechanism of action of these T-box transcription factors, on their target genes, on their role in cardiac morphogenesis, and on the regulation of their own expression. Tbx-factor target genes are identified by expression array analysis of transgenic mice. The regulation of the ANF gene, which is the best characterized marker for differentiating working myocardium and a Tbx-factor target gene, is being investigated. By coupling lineage marking to Tbx-gene or ANF expression (Cre-loxP), the lineage contributions of subpopulations of cardiac cells to the conduction system and other components of the heart is being investigated.

Team members

namefunction
Vincent ChristoffelsGroup Leader (PI)
Bjarke JensenScientist
Fernanda BosadaScientist
Rob JanssenScientist
Saritha AdepuScientist
Antoinette van OuwerkerkPhD student
Henk van WeerdPhD student
Ingeborg HooijkaasPhD student
Joyce ManPhD student
Karel van DuijvenbodenPhD student
Marie GunthelPhD student
Rajiv MohanPhD student
Vincent van EifPhD student
Corrie de Gier-de VriesTechnician
Vincent WakkerTechnician
Ben NelemansGuest
Gert van den BergGuest
Manuel SchmitzGuest
Theo SmitGuest
Inge DierxStudent
Jonathan KneepkensStudent

Key publications