Somites are segmented blocks of paraxial mesoderm that ultimately give rise to the vertebrae, skeletal muscle, cartilage and skin, among other tissues. The spatio-temporal dynamics of somite segmentation is driven by the synchronized oscillatory expression of Hes7; however, it has been difficult to study how this is regulated due to difficulties in imaging and manipulating the segmentation clock in vivo or in explanted tissue ex vivo. In this issue, Ryoichiro Kageyama and colleagues report a method to establish a mouse embryonic stem cell (mESC)-derived presomitic mesoderm-like tissue in which Hes7 expression oscillates like traveling waves, similar to its in vivo expression pattern. The authors build upon previous approaches by culturing the cells in low-adhesion plates to promote the formation of floating aggregates, and then modulate spatial variables such as colony size and well shape to determine the optimal parameters for Hes7 expression. Time-lapse imaging reveals not only wave-like synchronized Hes7 oscillations but also segmental boundary formation and reorganization of the anterior-posterior axis as a central-peripheral axis, as demonstrated by the expression pattern of the regional markers Mesp2 and Uncx4.1. Finally, the authors demonstrate the versatility of their system in a small-scale chemical-library screen and identify BET family proteins as important mediators in the synchronized expression of Hes7.
It's about time: a mESC-derived model of the segmentation clock
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It's about time: a mESC-derived model of the segmentation clock. Development 15 February 2018; 145 (4): e0401. doi:
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