New mechanisms of action of retinoic acid during post-implantational mouse embryogenesis

• Antragsteller: Dr. Ioan Ovidiu Sirbu
• Fachliche Zuordnung: Entwicklungsbiologie
• Förderung: Förderung von 2006 bis 2012
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 35368176

During early mouse embryogenesis, retinoic acid (RA, synthesized by Raldh2) signaling is necessary for axial elongation and is instrumental for coordination of several morphogenetic processes like neurulation, cardiogenesis, somitogenesis and limb budding. The complex phenotype of raldh2-/- embryo (axial truncation, open neural tube, expanded heart, small asymmetric somites, absence of limbs) is the result of profound deregulation of multiple signaling pathways like FGF, canonical and non-canonical (PCP) Wnt. Nevertheless, both the hierarchy between these signaling pathways and the precise molecular mechanisms of action of RA are far from being completely understood. By using a combined, knockdown and knockout approach, this study aims to re-define the role of RA as an integrator of multiple signaling pathways in the postimplantation embryo, by analyzing the role of Early Embryonic miRNA Cluster (EEmiRC) on mediating the response to RA signal during axial extension. In addition, we will explore new connections between RA, FGF, PCP and Wnt/beta-catenin signaling during trunck morphogenesis and neural tube closure. These results will extend our understanding of how RA signals to establish the correct body plan of mouse embryos.

• DFG-Verfahren: Sachbeihilfen