GSE120531
Identification and functional analysis of yap1b: a new Yap family member in teleosts that evolved a divergent transcriptional activation domain.
The vertebrate paralogs Yap1 and Taz are well known Hippo pathway effectors playing a key regulatory process in growth, morphogenesis, cell survival and cancer progression. Upon translocation to the nucleus Yap/Taz interact with Tead proteins and regulate transcription through their conserved C-terminal activation domain. Here we describe yap1b a new teleost paralog of the Yap1/Taz family that evolved specifically in Euteleostei -the largest clade within vertebrates- by duplication and subsequent adaptation of yap1. In contrast, taz paralogs were progressively lost in the Euteleostei lineage. We show that yap1b displays a unique C-terminal transcriptional activation domain that cannot be phosphorylated by kinases of the Src/Yes family. Using DamID-seq, we obtained comparative maps of yap1 and yap1b occupancy in the medaka genome during early embryogenesis; as well as of yap1 and taz in the zebrafish embryo. Our analyses show that both medaka paralogs target a largely overlapping set of genes. To further understand yap1b role, we mutated it by CRISPR-Cas9 in medaka. Yap1b mutants do not display any overt phenotype during embryogenesis or adulthood. However, yap1b mutation strongly enhances the early embryonic malformations described for medaka yap1 mutants. Thus yap1-/- ; yap1b-/- double mutants display more severe body flattening, eye misshaping, and increased apoptosis than yap1-/- single mutants. This negative epistatic interaction indicates overlapping gene functions between yap1 and yap1b. Taken together, our results indicate that, despite its divergent C-terminal transactivation domain, the newly evolved paralog yap1b cooperates with yap1 in regulating cell survival and tissue morphogenesis during early development. Overall design: iDamID-seq data from zebrafish and medaka late gastrula embryos, injected with DAM-zYAP1/DAM-zTAZ and DAM-mYAP1/DAM-mYAP1B mRNA, respectively, including their corresponding DAM-GFP control peaks.