Yap/Taz-TEAD activity links mechanical cues to progenitor cell behavior during zebrafish hindbrain segmentation

Abstract

Cells perceive their microenvironment through chemical and physical cues. However, how the mechanical signals are interpreted during embryonic tissue deformation to result in specific cell behaviors is largely unknown. 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, and to cell shape and actomyosin cytoskeletal changes. In this study, we demonstrate the role of Yap/Taz-TEAD activity as a sensor of mechanical signals in the regulation of the progenitor behavior of boundary cells during zebrafish hindbrain compartmentalization. Monitoring of in vivo Yap/Taz activity during hindbrain segmentation indicated that boundary cells responded to mechanical cues in a cellautonomous manner through Yap/Taz-TEAD activity. Cell-lineage analysis revealed that Yap/Taz-TEAD boundary cells decreased their proliferative activity when Yap/Taz-TEAD activity ceased, which preceded changes in their cell fate from proliferating progenitors to differentiated neurons. Functional experiments demonstrated the pivotal role of Yap/Taz-TEAD signaling in maintaining progenitor features in the hindbrain boundary cell population.

Cell-fate plasticity, adhesion and cell sorting complementarily establish a sharp midbrain-hindbrain boundary

“…Recently, actomyosin and Yap-mediated mechanisms have also been shown to be essential for maintaining rhombomere boundaries in zebrafish (Calzolari et al, 2014.,Voltes et al, 2019. However, our analysis with F-actin reporters and active Yap signaling reporter did not reveal any involvement during MHB formation (supplementary Fig S2).…”

Inter‐rhombomeric interactions reveal roles for fibroblast growth factors signaling in segmental regulation of EphA4 expression

“…These complementary domains of ligands and receptors set up bidirectional signaling interactions that govern cell sorting and adhesion in the hindbrain. Experiments have revealed that the Eph‐ephrin signaling system has a key role in restricting mixing of cells between rhombomeres and in the formation of rhombomeres boundaries …”

“…Experiments have revealed that the Eph-ephrin signaling system has a key role in restricting mixing of cells between rhombomeres [63][64][65][66][67] and in the formation of rhombomeres boundaries. 46,[68][69][70][71][72] Early in initiation of the segmentation cascade, signals adjacent to neural tissue along with signals within the neural epithelium play important roles in regulating the establishment of rhombomeres. 2,3,7,38,47 However, the degree to which signaling between rhombomeres participates in regulating segmental identity during hindbrain development is poorly understood.…”

Role of SHIP2 in cell repulsion regulated by Eph receptor and ephrin signaling

“…Forward signaling has a dominant role as it triggers strong repulsion (O’Neill et al, 2016; Rohani et al, 2011; Rohani et al, 2014; Taylor et al, 2017), but reverse signaling can also contribute (Wu et al, 2019). A further mechanism is important in epithelial tissues in which Eph receptor activation leads to actomyosin contraction that increases cortical tension at the interface (Calzolari et al, 2014; Cayuso et al, 2019; O’Neill et al, 2016; Voltes et al, 2019). This increase in cortical tension can drive cell segregation and act as a barrier to intermingling between Eph receptor and ephrin-expressing cells (Canty et al, 2017).…”