Objetivo
My lab is interested in the development of the tissue that gives rise to vertebrae and skeletal muscles called the paraxial mesoderm. A striking feature of this tissue is its segmental organization and we have made major contributions to the understanding of the molecular control of the segmentation process. We identified a molecular oscillator associated to the rhythmic production of somites and proposed a model for vertebrate segmentation based on the integration of a rhythmic signaling pulse gated spatially by a system of traveling FGF and Wnt signaling gradients. We are also studying the differentiation of paraxial mesoderm precursors into the muscle, cartilage and dermis lineages. Our work identified the Wnt, FGF and Notch pathways as playing a prominent role in the patterning and differentiation of paraxial mesoderm. In this application, we largely focus on the molecular control of paraxial mesoderm development. Using microarray and high throughput sequencing-based approaches and bioinformatics, we will characterize the transcriptional network acting downstream of Wnt, FGF and Notch in the presomitic mesoderm (PSM). We will also use genetic and pharmacological approaches utilizing real-time imaging reporters to characterize the pacemaker of the segmentation clock in vivo, and also in vitro using differentiated embryonic stem cells. We further propose to characterize in detail a novel RA-dependent pathway that we identified and which controls the somite left-right symmetry. Our work is expected to have a strong impact in the field of congenital spine anomalies, currently an understudied biomedical problem, and will be of utility in elucidating the etiology and eventual prevention of these disorders. This work is also expected to further our understanding of the Notch, Wnt, FGF and RA signalling pathways which are involved in segmentation and in the establishment of the vertebrate body plan, and which play important roles in a wide array of human diseases.
Convocatoria de propuestas
ERC-2009-AdG
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Régimen de financiación
ERC-AG - ERC Advanced GrantInstitución de acogida
67404 Illkirch Graffenstaden
Francia