A systems approach for assessing the interactions of muscle stem cells with their niche

 

G. Lavergne, B. Bertin, Y. Renaud

 

The understanding of the signals and intrinsic genetic determinants regulating the behaviour of muscle stem cells and their interactions with muscle niche represents a major challenge in developmental biology. Our experimental plan is designed to identify core genetic determinants of muscle stem cell-niche interactions applying a large set of genetic and imaging tools that allows following muscle stem cells in developing Drosophila embryos.

 

We will also apply cell- and time-specific translational profiling (TRAP method) of both the muscle stem cells and their muscle niche. Gained here knowledge will create a unique opportunity for uncovering genetic control of stem cell homing and niche-driven stem cell behavior.

 

In gene candidate approach strategy we will test Notch, Wingless/Wnt, EGF and FGF signalling pathways. We will use in vivo imaging (using our gapGFP and lifeAct-RFP sensor lines) to assess AMP cell shapes and their capacity to project filopodia/cytonemes and to contact surrounding muscles. The data that will be generated by this series of experiments will provide a complete overview on the activity of the key signalling pathways (timing and amplitude of activation) that play roles in muscle stem cell interactions with their niche. In genome-wide approach we will perform cell- and time-specific translational TRAP profiling using binary GAL4/UAS system for targeting polysomes of AMPs and three subpopulations of muscles (Lb-, Lms and slou-positive muscles) forming their niche. 

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