S21-03. The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass

Abstract In mammals, the first cell-fate decision occurs during preimplantation embryo development when the inner cell mass (ICM) and trophectoderm (TE) lineages are established. The ICM develops into the embryo proper, while the TE lineage forms the placenta. The underlying molecular mechanisms that govern lineage formation involve cell-to-cell interactions, cell polarization, cell signaling and transcriptional regulation. In this review, we will discuss the current understanding regarding the cellular and molecular events that regulate lineage formation in mouse preimplantation embryos with an emphasis on cell polarity and the Hippo signaling pathway. Moreover, we will provide an overview on some of the molecular tools that are used to manipulate the Hippo pathway and study cell-fate decisions in early embryos. Lastly, we will provide exciting future perspectives on transcriptional regulatory mechanisms that modulate the activity of the Hippo pathway in preimplantation embryos to ensure robust lineage segregation.

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A Comparative Analysis of Hippo Signaling Pathway Components during Murine and Bovine Early Mammalian Embryogenesis

Genes ◽

10.3390/genes12020281 ◽

2021 ◽

Vol 12 (2) ◽

pp. 281

Author(s):

Jyoti Sharma ◽

Monica Antenos ◽

Pavneesh Madan

Keyword(s):

Signaling Pathway ◽

Cell Mass ◽

Preimplantation Embryos ◽

Human Embryos ◽

Cell Contact ◽

Binding Motif ◽

Hippo Signaling ◽

Bovine Embryos ◽

Hippo Signaling Pathway ◽

Cell Cell

The time required for successful blastocyst formation varies among multiple species. The formation of a blastocyst is governed by numerous molecular cell signaling pathways, such as the Hippo signaling pathway. The Hippo signaling pathway is initiated by increased cell–cell contact and via apical polarity proteins (AMOT, PARD6, and NF2) during the period of preimplantation embryogenesis. Cell–cell contact and cell polarity activate (phosphorylates) the core cascade components of the pathway (mammalian sterile twenty like 1 and 2 (MST1/2) and large tumor suppressor 1 and 2 (LATS1/2)), which in turn phosphorylate the downstream effectors of the pathway (YAP1/TAZ). The Hippo pathway remains inactive with YAP1 (Yes Associated protein 1) present inside the nucleus in the trophectoderm (TE) cells (polar blastomeres) of the mouse blastocyst. In the inner cell mass (ICM) cells (apolar blastomeres), the pathway is activated with p-YAP1 present in the cytoplasm. On the contrary, during bovine embryogenesis, p-YAP1 is exclusively present in the nucleus in both TE and ICM cells. Contrary to mouse embryos, transcription co activator with PDZ-binding motif (TAZ) (also known as WWTR1) is also predominantly present in the cytoplasm in all the blastomeres during bovine embryogenesis. This review outlines the major differences in the localization and function of Hippo signaling pathway components of murine and bovine preimplantation embryos, suggesting significant differences in the regulation of this pathway in between the two species. The variance observed in the Hippo signaling pathway between murine and bovine embryos confirms that both of these early embryonic models are quite distinct. Moreover, based on the similarity of the Hippo signaling pathway between bovine and human early embryo development, bovine embryos could be an alternate model for understanding the regulation of the Hippo signaling pathway in human embryos.

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Lysophosphatidic Acid Accelerates Bovine In Vitro-Produced Blastocyst Formation through the Hippo/YAP Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22115915 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5915

Author(s):

Bo Yu ◽

Helena T. A. van Tol ◽

Christine H. Y. Oei ◽

Tom A. E. Stout ◽

Bernard A. J. Roelen

Keyword(s):

Signaling Pathway ◽

Lysophosphatidic Acid ◽

Inner Cell Mass ◽

Cell Mass ◽

Cell Lineage ◽

Hippo Signaling ◽

Blastocyst Formation ◽

Cdx2 Expression ◽

Gene And Protein Expression

The segregation of trophectoderm (TE) and inner cell mass in early embryos is driven primarily by the transcription factor CDX2. The signals that trigger CDX2 activation are, however, less clear. In mouse embryos, the Hippo-YAP signaling pathway is important for the activation of CDX2 expression; it is less clear whether this relationship is conserved in other mammals. Lysophosphatidic acid (LPA) has been reported to increase YAP levels by inhibiting its degradation. In this study, we cultured bovine embryos in the presence of LPA and examined changes in gene and protein expression. LPA was found to accelerate the onset of blastocyst formation on days 5 and 6, without changing the TE/inner cell mass ratio. We further observed that the expression of TAZ and TEAD4 was up-regulated, and YAP was overexpressed, in LPA-treated day 6 embryos. However, LPA-induced up-regulation of CDX2 expression was only evident in day 8 embryos. Overall, our data suggest that the Hippo signaling pathway is involved in the initiation of bovine blastocyst formation, but does not affect the cell lineage constitution of blastocysts.

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Hippo signaling pathway in mammals：a new therapeutic target for tumors

Hereditas (Beijing) ◽

10.3724/sp.j.1005.2012.00269 ◽

2012 ◽

Vol 34 (3) ◽

pp. 269-280 ◽

Cited By ~ 2

Author(s):

Chuan-Ming XU ◽

Fu-Sheng WAN

Keyword(s):

Signaling Pathway ◽

Therapeutic Target ◽

Hippo Signaling ◽

Hippo Signaling Pathway

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Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01830-z ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Xuehui Wang ◽

Changle Ji ◽

Jiashu Hu ◽

Xiaochong Deng ◽

Wenfang Zheng ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Cell Lines ◽

Luciferase Reporter ◽

Circular Rnas ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

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