Dual Specificity Phosphatase 7 Drives the Formation of Cardiac Mesoderm in Mouse Embryonic Stem Cells

Dual specificity phosphatase 7 (DUSP7) is a protein belonging to a broad group of phosphatases that 14 can dephosphorylate phosphoserine/phosphothreonine as well as phosphotyrosine residues within the 15 same substrate. DUSP7 has been linked to the negative regulation of mitogen activated protein kinases 16 (MAPK), and in particular to the regulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). 17 MAPKs play an important role in embryonic development, where their duration, magnitude, and 18 spatiotemporal activity must be strictly controlled by other proteins, among others by DUSPs. In this 19 study, we focused on the effect of DUSP7 depletion on the in vitro differentiation of mouse embryonic 20 stem (ES) cells. We showed that even though DUSP7 knock-out ES cells do retain some of their basic 21 characteristics, when it comes to differentiation, they preferentially differentiate towards neural cells, 22 while the formation of early cardiac mesoderm is repressed. Therefore, our data indicate that DUSP7 23 is necessary for the correct formation of neuroectoderm and cardiac mesoderm during the in vitro 24 differentiation of ES cells.