SUMMARY
How embryonic cells in vivo perceive their microenvironment through physical and mechanical cues during morphogenesis remains largely unexplored. Recently, the YAP/TAZ family of transcriptional co-activators has emerged as a fundamentally important regulator of cell proliferation and tissue regeneration, 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. We show that boundary cells respond to mechanical cues in a cell-autonomous manner through Yap/Taz-TEAD activity. Further, cell-lineage analysis reveals that Yap/Taz-TEAD active boundary cells display heterochronic proliferative capacity, and this switch in cell proliferation behavior results in changes of cell fate, from proliferating progenitors to differentiated neurons. Finally, functional experiments demonstrate the role of Yap/Taz-TEAD activity in maintaining the cell progenitor features in the hindbrain boundary cell population. Thus, our results suggest that changes in tissue architecture upon hindbrain segmentation work as informational systems affecting gene expression, and therefore cell fate during brain morphogenesis.