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

 

G. Lavergne, M. Zmojdzian, R. Aradhya

 

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 also observe muscle stem cell - motor neuron interactions which have impact on muscle innervation in embryos and on the other side play a role in maintenance of muscle stem cells in larval stages.

 

We are currently planning to apply single cell transcriptomic approaches to define gene expression signatures of both the muscle stem cells and their niche (muscle and neural cells). Gained here knowledge will create a unique opportunity for uncovering genetic control of stem cell homing and niche-driven stem cell behavior.

 

We previously demonstrated that ligand independent Notch signaling activated via Insulin pathway plays a crucial role in the reactivation of dormant AMPs (Aradhya, Zmojdzian et al., 2015)

Our recent data indicate that AMPs act as spatial and temporal check-points for navigating motor axons and are required for proper muscle innervation. We demonstrated that lateral AMPs interact with SNa and promote lateral SNa motor axon branching that ensures innervation of segmental border muscle (Lavergne et al., BioRxiv 2019, Development 2020).

We are planning to characterise L-AMP-SNa interactions at molecular levels (single cell approaches) to identify attractive cues. Our pleriminary data indicate the role of side step family of secreted molecules (Lavergne et al., BioRxiv 2019, Development 2020).

Aradhya, Zmojdzian et al., 2015, Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila. Elife Dec 9;4.

Lavergne et al., 2017, Characterization of Drosophila Muscle Stem Cell-Like Adult Muscle Precursors. Methods Mol Biol. 1556:103-116.

Lavergne et al., 2020, Drosophila adult muscle precursor cells contribute to motor axon pathfinding and proper innervation of embryonic muscles, Development in press

 

 

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