The Hippo signalling pathway has emerged as a key regulator of organ size, tissue homeostasis, and patterning. Recent studies have shown that two effectors in this pathway, YAP/TAZ, modulate Wnt/b-catenin signalling through their interaction with b-catenin or Dishevelled, depending on biological contexts. Here, we identify a novel mechanism through which Hippo signalling inhibits Wnt/b-catenin signalling. We show that YAP and TAZ, the transcriptional co-activators in the Hippo pathway, suppress Wnt signalling without suppressing the stability of b-catenin but through preventing its nuclear translocation. Our results show that YAP/TAZ binds to b-catenin, thereby suppressing Wnt-target gene expression, and that the Hippo pathway-stimulated phosphorylation of YAP, which induces cytoplasmic translocation of YAP, is required for the YAP-mediated inhibition of Wnt/b-catenin signalling. We also find that downregulation of Hippo signalling correlates with upregulation of b-catenin signalling in colorectal cancers. Remarkably, our analysis demonstrates that phosphorylated YAP suppresses nuclear translocation of b-catenin by directly binding to it in the cytoplasm. These results provide a novel mechanism, in which Hippo signalling antagonizes Wnt signalling by regulating nuclear translocation of b-catenin.

Cilia are essential for embryogenesis and maintenance of homeostasis, but little is known about the signalling pathways that regulate ciliogenesis. Here, we identify ERK7, an atypical mitogen-activated protein kinase, as a key regulator of ciliogenesis. ERK7 is strongly expressed in ciliated tissues of Xenopus embryos. ERK7 knockdown markedly diminishes both the number and the length of cilia in multiciliated cells, and it inhibits the apical migration of basal bodies. Moreover, ERK7 knockdown results in a loss of the apical actin meshwork, which is required for the proper migration of basal bodies. We find that the actin regulator CapZIP, which has been shown to regulate ciliogenesis in a phosphorylation-dependent manner, is an ERK7 substrate, and that Dishevelled, which has also been shown to regulate ciliogenesis, facilitates ERK7 phosphorylation of CapZIP through binding to both ERK7 and CapZIP. Collectively, these results identify an ERK7/Dishevelled/CapZIP axis that regulates ciliogenesis.

Retinoic acid (RA) signaling regulates a variety of developmental processes through controlling the expression of numerous genes. Here, we have identified and characterized RA‐responsive genes in mouse kidney development. Analysis of isolated embryonic kidneys cultured in the presence and absence of RA identified 33 candidates of RA‐responsive genes. Most of these candidate genes were down‐regulated by treatment with the RA receptor antagonist. Many of them have potential binding sites for Elf5, one of the RA‐responsive genes, in their promoter region. Whole‐mount in situ hybridization showed that specific expression of Elf5 in the ureteric trunk depends on RA. RA‐dependent expression in the ureteric trunk was also showed for the sodium channel subunit Scnn1b, which has been shown to be the marker gene of the collecting duct. In contrast, the expression of Ecm1, Tnfsf13b and IL‐33 was detected in the stromal mesenchymal cells. Both Tnfsf13b and IL‐33 were previously shown to cause nuclear factor κB (NF‐κB) activation. We have showed that the inhibition of NF‐κB signaling with specific inhibitors suppresses branching morphogenesis of the ureteric bud. Our study thus identifies and characterizes RA‐dependent up‐regulated genes in kidney development, and suggests an involvement of NF‐κB signaling in the branching morphogenesis.

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Background: HIRA is a conserved histone chaperone required for regulation of chromatin structure. Results: Genes that encode HIRA proteins are responsible for cross-tolerance. Specifically, stress-responsive gene expression was most profoundly compromised in HIRA disruptants. Conclusion: HIRA is involved in cross-tolerance via regulation of stress-responsive gene expression. Significance: This study provides evidence that fission yeast HIRA functions in stress response.