Mutual regulation between Hippo signaling and actin cytoskeleton

Matsui, Yurika; Lai, Zhi Chun

doi:10.1007/s13238-013-3084-z

Cited by 43 publications

(32 citation statements)

References 25 publications

(54 reference statements)

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“…In some developmental contexts, F-actin negatively regulates HIPPO signaling (Matsui and Lai, 2013). Interestingly, we and others have observed that F-actin is disorganized in PARD6B KD and TFAP2C KD morulae (Alarcon, 2010;Choi et al, 2012).…”

Section: Discussionmentioning

confidence: 57%

Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage

et al. 2015

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Cell fate decisions are fundamental to the development of multicellular organisms. In mammals the first cell fate decision involves segregation of the pluripotent inner cell mass and the trophectoderm, a process regulated by cell polarity proteins, HIPPO signaling and lineagespecific transcription factors such as CDX2. However, the regulatory mechanisms that operate upstream to specify the trophectoderm lineage have not been established. Here we report that transcription factor AP-2γ (TFAP2C) functions as a novel upstream regulator of Cdx2 expression and position-dependent HIPPO signaling in mice. Loss-and gain-of-function studies and promoter analysis revealed that TFAP2C binding to an intronic enhancer is required for activation of Cdx2 expression during early development. During the 8-cell to morula transition TFAP2C potentiates cell polarity to suppress HIPPO signaling in the outside blastomeres. TFAP2C depletion triggered downregulation of PARD6B, loss of apical cell polarity, disorganization of F-actin, and activation of HIPPO signaling in the outside blastomeres. Rescue experiments using Pard6b mRNA restored cell polarity but only partially corrected position-dependent HIPPO signaling, suggesting that TFAP2C negatively regulates HIPPO signaling via multiple pathways. Several genes involved in regulation of the actin cytoskeleton (including Rock1, Rock2) were downregulated in TFAP2C-depleted embryos. Inhibition of ROCK1 and ROCK2 activity during the 8-cell to morula transition phenocopied TFAP2C knockdown, triggering a loss of position-dependent HIPPO signaling and decrease in Cdx2 expression. Altogether, these results demonstrate that TFAP2C facilitates trophectoderm lineage specification by functioning as a key regulator of Cdx2 transcription, cell polarity and position-dependent HIPPO signaling.

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Section: Discussionmentioning

confidence: 57%

Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage

et al. 2015

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“…RhoA activates LIMK through ROCK, and Rac1 stimulates this kinase through PAK (reviewed in (Bar-Sagi and Hall, 2000; Radu et al, 2014), which can explain why ROCK inhibitors do not prevent the activation of YAP by the latter. In turn, how F-actin stimulates YAP was unclear (reviewed in (Matsui and Lai, 2013). YAP is part of multiple cytosolic protein complexes, many of which are driven by the direct interaction between the WW domains of YAP with the PPxY motifs present in most of its associated proteins, including LATS and AMOT (Sudol, 2013; Sudol et al, 2012; Wang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Hippo-Independent Activation of YAP by the GNAQ Uveal Melanoma Oncogene through a Trio-Regulated Rho GTPase Signaling Circuitry

et al. 2014

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Summary Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ~83% and ~6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional co-activator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of PLCβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, the first described GNAQ/GNA11-initiated human malignancy.

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“…The actin cytoskeleton has been linked to Hippo signaling (Matsui and Lai, 2013). For example, F-actin regulates Hippo pathway and cell proliferation in the Drosophila wing imaginal disc (Fernández et al, 2011; Sansores-Garcia et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Yorkie regulates epidermal wound healing in Drosophila larvae independently of cell proliferation and apoptosis

Tsai

Anderson

Burra

et al. 2017

Developmental Biology

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Yorkie (Yki), the transcriptional co-activator of the Hippo signaling pathway, has well-characterized roles in balancing apoptosis and cell division during organ growth control. Yki is also required in diverse tissue regenerative contexts. In most cases this requirement reflects its well-characterized roles in balancing apoptosis and cell division. Whether Yki has repair functions outside of the control of cell proliferation, death, and growth is not clear. Here we show that Yki and Scalloped (Sd) are required for epidermal wound closure in the Drosophila larval epidermis. Using a GFP-tagged Yki transgene we show that Yki transiently translocates to some epidermal nuclei upon wounding. Genetic analysis strongly suggests that Yki interacts with the known wound healing pathway, Jun N-terminal kinase (JNK), but not with Platelet Derived Growth Factor/Vascular-Endothelial Growth Factor receptor (Pvr). Yki likely acts downstream of or parallel to JNK signaling and does not appear to regulate either proliferation or apoptosis in the larval epidermis during wound repair. Analysis of actin structures after wounding suggests that Yki and Sd promote wound closure through actin regulation. In sum, we found that Yki regulates an epithelial tissue repair process independently of its previously documented roles in balancing proliferation and apoptosis.

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Mutual regulation between Hippo signaling and actin cytoskeleton

Cited by 43 publications

References 25 publications

Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage

Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage

Hippo-Independent Activation of YAP by the GNAQ Uveal Melanoma Oncogene through a Trio-Regulated Rho GTPase Signaling Circuitry

Yorkie regulates epidermal wound healing in Drosophila larvae independently of cell proliferation and apoptosis

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