YAP/TAZ-TEAD Activity Links Mechanical Cues To Specific Cell Fate Within The Hindbrain Boundaries

How embryonic cells perceive their microenvironment through physical/mechanical cues during morphogenesis remains largely unexplored. The YAP/TAZ family has emerged as a fundamentally important regulator of cell proliferation, responding to cues from the extracellular matrix, cell shape and the actomyosin cytoskeleton. However, how signals are interpreted during embryonic tissue deformation resulting in specific cell fates has not been solved yet. In this work, we use the zebrafish hindbrain to explore how changes in tissue architecture during tissue segmentation affect gene expression and thereby ultimately inform cell decisions. We unveil the role of Yap/Taz-TEAD activity in hindbrain boundaries as sensor and effector of mechanical signals in the regulation of cell fate upon hindbrain compartmentalization, and show that boundary cells respond to mechanical cues cell-autonomously through Yap/Taz-TEAD-activity. Further, cell-lineage analysis reveals that Yap/Taz-TEAD boundary cells display heterochronic proliferative capacity, and this switch in cell proliferation results in cell fate changes, from proliferating progenitors to differentiated neurons. Finally, we demonstrate the role of Yap/Taz-TEAD activity in maintaining the cell progenitor features in the hindbrain boundary cell population.