YAP/TAZ-TEAD Activity Links Mechanical Cues To Cell Progenitor Behavior During Hindbrain Segmentation
Adrià VoltesiD, Covadonga F. HeviaiD, Carolyn Engel-PizcuetaiD, Chaitanya DingareiD, Simone Calzolari, Javier TerrienteiD, Caren NordeniD, Virginie LecaudeyiD, Cristina PujadesiD
Abstract
Cells perceive their microenvironment through chemical and physical cues. However, how mechanical signals are interpreted during embryonic tissue deformation resulting in specific cell behaviors is largely unexplored. The Yap/Taz family of transcriptional co-activators has emerged as an important regulator of tissue growth and regeneration, responding to physical cues from the extracellular matrix, cell shape and actomyosin cytoskeleton. In this work, we unveiled the role of Yap/Taz-TEAD activity as sensor of mechanical signals in the regulation of the progenitor behavior of boundary cells during hindbrain compartmentalization. Monitoring in vivo Yap/Taz-activity during hindbrain segmentation we discovered that boundary cells respond to mechanical cues in a cell-autonomous manner through Yap/Taz-TEAD activity. Cell-lineage analysis revealed that Yap/Taz-TEAD boundary cells decrease their proliferative activity when Yap/Taz-TEAD ceased, preceding changes of cell fate: from proliferating progenitors to differentiated neurons. Functional experiments demonstrated the pivotal role of Yap/Taz-TEAD signaling in maintaining the progenitor features in the hindbrain boundary cell population.
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