Yap1b, a divergent Yap/Taz family member, cooperates with yap1 in survival and morphogenesis via common transcriptional targets

Abstract

Yap1/Taz are well-known Hippo effectors triggering complex transcriptional programs controlling growth, survival, and cancer progression. Here we describe yap1b, a new Yap1/Taz family member with a unique transcriptional activation domain that cannot be phosphorylated by Src/Yes kinases. We show that yap1b evolved specifically in euteleosts (i.e. including medaka but not zebrafish) by duplication and adaptation of yap1. Using DamID-seq we generated maps of chromatin occupancy for Yap1, Taz (Wwtr1), and Yap1b, in gastrulating zebrafish and medaka embryos. Our comparative analyses uncover the genetic programs controlled by yap family proteins during early embryogenesis, and show largely overlapping targets for Yap1 and Yap1b. CRISPR/Cas9-induced mutation of yap1b in medaka does not result in an overt phenotype during embryogenesis or adulthood. However, yap1b mutation strongly enhances the embryonic malformations observed in yap1 mutants. Thus yap1−/−; yap1b−/− double mutants display more severe body flattening, eye misshaping, and increased apoptosis than yap1−/− single mutants; thus revealing overlapping gene functions. Our results indicate that, despite its divergent transactivation domain, Yap1b cooperates with Yap1 to regulate cell survival and tissue morphogenesis during early development.

The Shh / Gli3 gene regulatory network precedes the origin of paired fins and reveals the deep homology between distal fins and digits

“…Fish Stocks. Medaka WT (iCab) and ZRS+sZRS KO [Δ3.4kb (20)] strains were maintained and bred under standard conditions (32). Embryos were staged in The Shh/Gli3 gene regulatory network precedes the origin of paired fins and reveals the deep homology between distal fins and digits hours postfertilization as previously described (33).…”

Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish

“…krt5, krt8, and krt97), and desmosomal genes (e.g. evpla, pleca, plecb, and ppl) have been identified as targets for Yap/Tead complexes by ChIP-seq studies in mammalian cells (Estaras, et al, 2017;Zanconato, et al, 2015;Lian, et al, 2010), as well as DamID-seq studies in zebrafish embryos (Vazquez-Marin, et al, 2019). Thus, the direct transcriptional regulation of keratins and plaque genes by Yap/Tead complexes seems a conserved theme across different tissues and vertebrate species.…”

“…Concentration of the RNA samples was evaluated by Qubit (Thermo Fisher), and then the samples were used for subsequent applications. qPCR cDNA retrotranscription and qPCR were performed as described (Vazquez-Marin, et al, 2019).…”

The S-phase-induced lncRNA SUNO1 promotes cell proliferation by controlling YAP1/Hippo signaling pathway

“…We consistently observed reduced mRNA and protein levels of YAP1 in SUNO1 -depleted cells ( Figure 4B–C ). A recent study indicated that YAP1 positively autoregulates its own expression ( Vázquez-Marín et al, 2019 ). In support of this observation, YAP1 promoter contains several TEAD4 binding sites (data not shown), implying that YAP1 expression could be regulated by TEAD/YAP1 axes.…”