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AXIAL.EC

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PRINCIPLES OF AXIAL POLARITY DRIVEN VASCULAR PATTERNING
The formation of a functional patterned vascular network is essential for development, tissue growth and organ physiology. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malf... The formation of a functional patterned vascular network is essential for development, tissue growth and organ physiology. Several human vascular disorders arise from the mis-patterning of blood vessels, such as arteriovenous malformations, aneurysms and diabetic retinopathy. Although blood flow is recognised as a stimulus for vascular patterning, very little is known about the molecular mechanisms that regulate endothelial cell behaviour in response to flow and promote vascular patterning. Recently, we uncovered that endothelial cells migrate extensively in the immature vascular network, and that endothelial cells polarise against the blood flow direction. Here, we put forward the hypothesis that vascular patterning is dependent on the polarisation and migration of endothelial cells against the flow direction, in a continuous flux of cells going from low-shear stress to high-shear stress regions. We will establish new reporter mouse lines to observe and manipulate endothelial polarity in vivo in order to investigate how polarisation and coordination of endothelial cells movements are orchestrated to generate vascular patterning. We will manipulate cell polarity using mouse models to understand the importance of cell polarisation in vascular patterning. Also, using a unique zebrafish line allowing analysis of endothelial cell polarity, we will perform a screen to identify novel regulators of vascular patterning. Finally, we will explore the hypothesis that defective flow-dependent endothelial polarisation underlies arteriovenous malformations using two genetic models. This integrative approach, based on high-resolution imaging and unique experimental models, will provide a unifying model defining the cellular and molecular principles involved in vascular patterning. Given the physiological relevance of vascular patterning in health and disease, this research plan will set the basis for the development of novel clinical therapies targeting vascular disorders. ver más
28/02/2022
iMM
2M€
Perfil tecnológico estimado
Duración del proyecto: 72 meses Fecha Inicio: 2016-02-23
Fecha Fin: 2022-02-28

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2022-02-28
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-StG-2015: ERC Starting Grant
Cerrada hace 9 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANT... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5