Cécile Duplàa

Our challenge was to define the nature of the Wnt signaling pathways and the molecular effectors acting during vascular morphogenesis. In vertebrates, blood vessels form stereotyped, hierarchical, branched networks. Mutations in the genes of the Wnt pathway in the endothelium have been shown to be associated with damage to the vascular networks and ultimately to the progression of vascular diseases. Our pioneer studies have identified that Frizzled receptors participate in the maintenance of vascular integrity. We then reported the role of the Wnt/non canonical planar cell polarity (PCP) signaling on vascular remodeling during development and in pathological ischemic cerebral disease. Lately, we have postulated that brain and heart pathologies have a common denominator: small vessel damage. These projects were developed by combining the use of original specific conditional mutants, functional approaches and pathological models, as dementia induced by chronic cerebral hypoperfusion and a model of heart failure with preserved ejection fraction. We focus now on the search of new determinants of brain small vessel disease. It is of major interest to delineate signaling pathways regulating the physiological functions of the neurovascular unit and gain insights into the pathological conditions causing loss or breakdown of cerebral vessels.