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Hearts and limbs: Linking morphometrics with 3D analysis of gene expression patterns (3D Gene Shape)
Date du début: 1 mai 2013, Date de fin: 9 août 2016 PROJET  TERMINÉ 

Development of new imaging techniques, such as optical projection tomography (OPT), to visualize gene expression patterns within developing structures in a 3D framework has revolutionized developmental biology research. However, methods to precisely quantify these 3D expression distributions in a systematic manner are still lacking. We are developing a novel approach to combine OPT with Geometric Morphometrics (GM) methods to quantify the relationship between morphology and gene expression shape patterns. Here we propose a biologically-oriented extension to this project that involves embryonic phenotyping of the heart and limb of control and mutant littermates of an Apert syndrome mouse model. Apert syndrome is a rare congenital disease caused by one of two mutations in fibroblast growth factor (Fgf) receptor 2 that presents with severe craniofacial malformations, as well as other developmental defects, including heart and limb defects. The use of such mouse model will enable us to apply the OPT-GM approach to two different organs, by quantifying heart and limb shape in association with gene expression shape patterns of Fgf downstream genes at an early and a late stage of development. Comparison between control and mutant littermates will reveal differences in normal and disease-altered patterns of development, allowing us to describe exactly what has gone wrong during development, both at an anatomical and molecular level. These results will provide a better understanding of limb and cardiac morphogenesis, which can be further used in biomedical research of many congenital diseases, including congenital heart disease, which is the most common of human birth defects. Our goal is to demonstrate that the combined application of OPT-GM methods for fast and accurate phenotyping is relevant to many organs, will increase our ability to reveal defects in embryonic development and will thus have multiple applications in medicine, featuring a significant advance in biology.