Project Details
Projekt
Role of Caspase-8 and FLIP protein complexes in developmental angiogenesis
Subject Area
Developmental Biology
Cell Biology
Cell Biology
Term
from 2014 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 267092730
Formation of a functional vascular system occurs by the combination of blood vessel assembly, growth and guidance, maturation and remodeling. Despite the increased knowledge of the mechanisms controlling blood vessel growth, the mechanisms that regulate vessel remodeling and maturation are still rather unknown. In this context, several studies indicate that apoptosis (programmed cell death) in endothelial cells (ECs) contributes, at least partially, to the process of vascular remodeling and pruning under physiological conditions. Still, there is little information about the molecular mechanisms regulating this physiological process of EC cell death in vivo. Several recent studies support the concept that molecules initially found to have a role in apoptosis (such as death ligands/receptors, caspases or Bcl-2 pro-apoptotic proteins) have also apoptotic-independent functions in physiological conditions. In this respect, mice deficient for the adaptor molecule FADD, the pro-apoptotic Caspase-8 or the apoptosis regulator FLIP, are embryonically lethal due to a failure in yolk sac vascularization rather than to a lack of cell death. Thus, suggesting the existence of additional non-apoptotic functions (possibly vascular) for these proteins. The main goal of this project is to understand the possible pro-angiogenic (in vessel sprouting) and apoptotic (in vessel remodeling) functions of Casp-8 and FLIP in the vascular system during developmental angiogenesis using as model systems the developing mouse retina and brain. For this, we propose three complementary aims using a combination of in vivo mouse genetics, in vitro cell culture angiogenic assays and biochemistry approaches. Results in this project will provide new insights into the cellular and molecular mechanisms of blood vessel growth and remodeling. In addition, this project will also bring new knowledge into the non-apoptotic roles of classical cell death molecules in the vascular system.
DFG Programme
Research Grants
