Developmental Signals - Hippo - Revision history

Z8600021 at 18:01, 4 July 2022

2022-07-04T18:01:53Z

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	* '''Cyclin-Dependent Kinase 7 [https://www.omim.org/entry/601955 CDK7] regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus'''{{#pmid:31857346\|PMID31857346}} "Hippo signaling controls organ size and tumor progression through a conserved pathway leading to nuclear translocation of the transcriptional effector Yki/Yap/Taz. Most of our understanding of Hippo signaling pertains to its cytoplasmic regulation, but how the pathway is controlled in the nucleus remains poorly understood. Here we uncover an evolutionarily conserved mechanism by which CDK7 promotes Yki/Yap/Taz stabilization in the nucleus to sustain Hippo pathway outputs. We found that a modular E3 ubiquitin ligase complex CRL4DCAF12 binds and targets Yki/Yap/Taz for ubiquitination and degradation, whereas CDK7 phosphorylates Yki/Yap/Taz at S169/S128/S90 to inhibit CRL4DCAF12 recruitment, leading to Yki/Yap/Taz stabilization. As a consequence, inactivation of CDK7 reduced organ size and inhibited tumor growth, which could be reversed by restoring Yki/Yap activity. Our study identifies an unanticipated layer of Hippo pathway regulation, defines a novel mechanism by which CDK7 regulates tissue growth, and implies CDK7 as a drug target for Yap/Taz-driven cancer." [https://www.omim.org/entry/601955 OMIM - CDK7]		* '''Cyclin-Dependent Kinase 7 [https://www.omim.org/entry/601955 CDK7] regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus'''{{#pmid:31857346\|PMID31857346}} "Hippo signaling controls organ size and tumor progression through a conserved pathway leading to nuclear translocation of the transcriptional effector Yki/Yap/Taz. Most of our understanding of Hippo signaling pertains to its cytoplasmic regulation, but how the pathway is controlled in the nucleus remains poorly understood. Here we uncover an evolutionarily conserved mechanism by which CDK7 promotes Yki/Yap/Taz stabilization in the nucleus to sustain Hippo pathway outputs. We found that a modular E3 ubiquitin ligase complex CRL4DCAF12 binds and targets Yki/Yap/Taz for ubiquitination and degradation, whereas CDK7 phosphorylates Yki/Yap/Taz at S169/S128/S90 to inhibit CRL4DCAF12 recruitment, leading to Yki/Yap/Taz stabilization. As a consequence, inactivation of CDK7 reduced organ size and inhibited tumor growth, which could be reversed by restoring Yki/Yap activity. Our study identifies an unanticipated layer of Hippo pathway regulation, defines a novel mechanism by which CDK7 regulates tissue growth, and implies CDK7 as a drug target for Yap/Taz-driven cancer." [https://www.omim.org/entry/601955 OMIM - CDK7]

	* '''Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse'''{{#pmid:26902285\|PMID26902285}} "In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture."

	* '''Review - Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos'''{{#pmid:25986053\|PMID25986053}} "During the preimplantation stage, mouse embryos establish two cell lineages by the time of early blastocyst formation: the trophectoderm (TE) and the inner cell mass (ICM). Historical models have proposed that the establishment of these two lineages depends on the cell position within the embryo (e.g., the positional model) or cell polarization along the apicobasal axis (e.g., the polarity model). Recent findings have revealed that the Hippo signaling pathway plays a central role in the cell fate-specification process: active and inactive Hippo signaling in the inner and outer cells promote ICM and TE fates, respectively. Intercellular adhesion activates, while apicobasal polarization suppresses Hippo signaling, and a combination of these processes determines the spatially regulated activation of the Hippo pathway in 32-cell-stage embryos. Therefore, there is experimental evidence in favor of both positional and polarity models. At the molecular level, phosphorylation of the Hippo-pathway component angiomotin at adherens junctions (AJs) in the inner (apolar) cells activates the Lats protein kinase and triggers Hippo signaling. In the outer cells, however, cell polarization sequesters Amot from basolateral AJs and suppresses activation of the Hippo pathway. Other mechanisms, including asymmetric cell division and Notch signaling, also play important roles in the regulation of embryonic development. In this review, I discuss how these mechanisms cooperate with the Hippo signaling pathway during cell fate-specification processes." [[Developmental Signals - Notch]] \| [[Mouse Development]]

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	\| {{Older papers}}		\| {{Older papers}}
			* '''Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse'''{{#pmid:26902285\|PMID26902285}} "In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture."

			* '''Review - Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos'''{{#pmid:25986053\|PMID25986053}} "During the preimplantation stage, mouse embryos establish two cell lineages by the time of early blastocyst formation: the trophectoderm (TE) and the inner cell mass (ICM). Historical models have proposed that the establishment of these two lineages depends on the cell position within the embryo (e.g., the positional model) or cell polarization along the apicobasal axis (e.g., the polarity model). Recent findings have revealed that the Hippo signaling pathway plays a central role in the cell fate-specification process: active and inactive Hippo signaling in the inner and outer cells promote ICM and TE fates, respectively. Intercellular adhesion activates, while apicobasal polarization suppresses Hippo signaling, and a combination of these processes determines the spatially regulated activation of the Hippo pathway in 32-cell-stage embryos. Therefore, there is experimental evidence in favor of both positional and polarity models. At the molecular level, phosphorylation of the Hippo-pathway component angiomotin at adherens junctions (AJs) in the inner (apolar) cells activates the Lats protein kinase and triggers Hippo signaling. In the outer cells, however, cell polarization sequesters Amot from basolateral AJs and suppresses activation of the Hippo pathway. Other mechanisms, including asymmetric cell division and Notch signaling, also play important roles in the regulation of embryonic development. In this review, I discuss how these mechanisms cooperate with the Hippo signaling pathway during cell fate-specification processes." [[Developmental Signals - Notch]] \| [[Mouse Development]]

	* '''{{YAP}} is essential for tissue tension to ensure vertebrate 3D body shape'''{{#pmid:25778702\|PMID25778702}} "Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape." [[Medaka Development]]		* '''{{YAP}} is essential for tissue tension to ensure vertebrate 3D body shape'''{{#pmid:25778702\|PMID25778702}} "Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape." [[Medaka Development]]

Z8600021 at 18:00, 4 July 2022

2022-07-04T18:00:51Z

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			* '''Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation'''{{#pmid:35451959\|PMID35451959}} "The Hippo pathway, a highly conserved signaling cascade that functions as an integrator of molecular signals and biophysical states, ultimately impinges upon the transcription coactivator Yes-associated protein 1 (YAP). Hippo-YAP signaling has been shown to play key roles both at the early embryonic stages of {{implantation}} and {{gastrulation}}, and later during neurogenesis. To explore YAP's potential role in neurulation, we used self-organizing neuruloids grown from human embryonic stem cells on micropatterned substrates. We identified YAP activation as a key lineage determinant, first between neuronal {{ectoderm}} and nonneuronal {{ectoderm}}, and later between epidermis and neural crest, indicating that YAP activity can enhance the effect of {{BMP4}} stimulation and therefore affect ectodermal specification at this developmental stage. Because aberrant Hippo-YAP signaling has been implicated in the pathology of Huntington's Disease (HD), we used isogenic mutant neuruloids to explore the relationship between signaling and the disease. We found that HD neuruloids demonstrate ectopic activation of gene targets of YAP and that pharmacological reduction of YAP's transcriptional activity can partially rescue the HD phenotype."

	* '''Deletion of Nf2 in {{neural crest}}-derived {{tongue}} mesenchyme alters tongue shape and size, Hippo signalling and cell proliferation in a region- and stage-specific manner'''{{#pmid:34697858\|PMID34697858}} "The mammalian tongue develops from the branchial arches (1-4) and comprises highly organized tissues compartmentalized by mesenchyme/connective tissue that is largely derived from neural crest (NC). This study aimed to understand the roles of tumour suppressor Neurofibromin 2 (Nf2) in NC-derived tongue mesenchyme in regulating Hippo signalling and cell proliferation for the proper development of tongue shape and size. ...Specifically, at {{ME12.5}} Nf2cKO mutants had a decreased level of Hippo signalling transcription factor Yes-associated protein (Yap), Yap target genes and cell proliferation anteriorly, while having an increased Yap, Yap target genes and cell proliferation posteriorly, which lead to a tip-pointed and posteriorly widened tongue. At {{ME15.5}}, loss of Nf2 in the NC lineage resulted in distinct changes in cell proliferation in different regions, that is, high in epithelium and mesenchyme subjacent to the epithelium, and lower in deeper layers of the mesenchyme. At {{ME18.5}}, cell proliferation was reduced throughout the Nf2cKO tongue."		* '''Deletion of Nf2 in {{neural crest}}-derived {{tongue}} mesenchyme alters tongue shape and size, Hippo signalling and cell proliferation in a region- and stage-specific manner'''{{#pmid:34697858\|PMID34697858}} "The mammalian tongue develops from the branchial arches (1-4) and comprises highly organized tissues compartmentalized by mesenchyme/connective tissue that is largely derived from neural crest (NC). This study aimed to understand the roles of tumour suppressor Neurofibromin 2 (Nf2) in NC-derived tongue mesenchyme in regulating Hippo signalling and cell proliferation for the proper development of tongue shape and size. ...Specifically, at {{ME12.5}} Nf2cKO mutants had a decreased level of Hippo signalling transcription factor Yes-associated protein (Yap), Yap target genes and cell proliferation anteriorly, while having an increased Yap, Yap target genes and cell proliferation posteriorly, which lead to a tip-pointed and posteriorly widened tongue. At {{ME15.5}}, loss of Nf2 in the NC lineage resulted in distinct changes in cell proliferation in different regions, that is, high in epithelium and mesenchyme subjacent to the epithelium, and lower in deeper layers of the mesenchyme. At {{ME18.5}}, cell proliferation was reduced throughout the Nf2cKO tongue."

Z8600021 at 03:01, 23 February 2022

2022-02-23T03:01:52Z

← Older revision		Revision as of 14:01, 23 February 2022
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			* '''Deletion of Nf2 in {{neural crest}}-derived {{tongue}} mesenchyme alters tongue shape and size, Hippo signalling and cell proliferation in a region- and stage-specific manner'''{{#pmid:34697858\|PMID34697858}} "The mammalian tongue develops from the branchial arches (1-4) and comprises highly organized tissues compartmentalized by mesenchyme/connective tissue that is largely derived from neural crest (NC). This study aimed to understand the roles of tumour suppressor Neurofibromin 2 (Nf2) in NC-derived tongue mesenchyme in regulating Hippo signalling and cell proliferation for the proper development of tongue shape and size. ...Specifically, at {{ME12.5}} Nf2cKO mutants had a decreased level of Hippo signalling transcription factor Yes-associated protein (Yap), Yap target genes and cell proliferation anteriorly, while having an increased Yap, Yap target genes and cell proliferation posteriorly, which lead to a tip-pointed and posteriorly widened tongue. At {{ME15.5}}, loss of Nf2 in the NC lineage resulted in distinct changes in cell proliferation in different regions, that is, high in epithelium and mesenchyme subjacent to the epithelium, and lower in deeper layers of the mesenchyme. At {{ME18.5}}, cell proliferation was reduced throughout the Nf2cKO tongue."

	* '''Pivotal role of the transcriptional co-activator YAP in trophoblast stemness of the developing human placenta''' [https://www.pnas.org/content/117/24/13562.abstract?etoc PMAS] "Defects in development and differentiation of the placenta are associated with various pregnancy disorders such as miscarriage, stillbirth, preeclampsia, and intrauterine growth restriction. However, our knowledge on critical regulators of human placentation is scarce. In the present study, we show that the Hippo signaling-dependent transcriptional coactivator YAP plays a pivotal role in the maintenance of proliferative trophoblasts, the epithelial cells of the placenta. By binding to the transcription factor TEAD4, YAP stimulates expression of genes promoting trophoblast stemness. Additionally, YAP–TEAD4 complexes actively repress genes associated with the differentiated syncytiotrophoblast, the hormone-secreting cell type of the human placenta. Hence, YAP orchestrates a complex developmental program ensuring growth and expansion of the human placenta. we herein show that YAP, the transcriptional coactivator of the Hippo signaling pathway, promotes maintenance of cytotrophoblast progenitors by different genomic mechanisms. Genetic or chemical manipulation of YAP in these cellular models revealed that it stimulates proliferation and expression of cell cycle regulators and stemness-associated genes, but inhibits cell fusion and production of syncytiotrophoblast (STB)-specific proteins, such as hCG and GDF15."		* '''Pivotal role of the transcriptional co-activator YAP in trophoblast stemness of the developing human placenta''' [https://www.pnas.org/content/117/24/13562.abstract?etoc PMAS] "Defects in development and differentiation of the placenta are associated with various pregnancy disorders such as miscarriage, stillbirth, preeclampsia, and intrauterine growth restriction. However, our knowledge on critical regulators of human placentation is scarce. In the present study, we show that the Hippo signaling-dependent transcriptional coactivator YAP plays a pivotal role in the maintenance of proliferative trophoblasts, the epithelial cells of the placenta. By binding to the transcription factor TEAD4, YAP stimulates expression of genes promoting trophoblast stemness. Additionally, YAP–TEAD4 complexes actively repress genes associated with the differentiated syncytiotrophoblast, the hormone-secreting cell type of the human placenta. Hence, YAP orchestrates a complex developmental program ensuring growth and expansion of the human placenta. we herein show that YAP, the transcriptional coactivator of the Hippo signaling pathway, promotes maintenance of cytotrophoblast progenitors by different genomic mechanisms. Genetic or chemical manipulation of YAP in these cellular models revealed that it stimulates proliferation and expression of cell cycle regulators and stemness-associated genes, but inhibits cell fusion and production of syncytiotrophoblast (STB)-specific proteins, such as hCG and GDF15."

Z8600021 at 00:13, 17 Haziran 2020

2020-06-17T00:13:20Z

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	:'''Links:''' [~~[Blastocyst]~~]		:'''Links:''' {{Blastocyst}}

			===Trophoblast===

			'''Pivotal role of the transcriptional co-activator YAP in trophoblast stemness of the developing human placenta''' [https://www.pnas.org/content/117/24/13562.abstract?etoc PMAS] "Defects in development and differentiation of the placenta are associated with various pregnancy disorders such as miscarriage, stillbirth, preeclampsia, and intrauterine growth restriction. However, our knowledge on critical regulators of human placentation is scarce. In the present study, we show that the Hippo signaling-dependent transcriptional coactivator YAP plays a pivotal role in the maintenance of proliferative {{trophoblast}}s, the epithelial cells of the placenta. By binding to the transcription factor TEAD4, YAP stimulates expression of genes promoting trophoblast stemness. Additionally, YAP–TEAD4 complexes actively repress genes associated with the differentiated {{syncytiotrophoblast}}, the hormone-secreting cell type of the human placenta. Hence, YAP orchestrates a complex developmental program ensuring growth and expansion of the human placenta. we herein show that YAP, the transcriptional coactivator of the Hippo signaling pathway, promotes maintenance of {{cytotrophoblast}} progenitors by different genomic mechanisms. Genetic or chemical manipulation of YAP in these cellular models revealed that it stimulates proliferation and expression of cell cycle regulators and stemness-associated genes, but inhibits cell fusion and production of syncytiotrophoblast (STB)-specific proteins, such as hCG and GDF15."

			:'''Links:''' {{trophoblast}}

	==Bone==		==Bone==

Z8600021 at 00:11, 17 Haziran 2020

2020-06-17T00:11:38Z

← Older revision		Revision as of 11:11, 17 Haziran 2020
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			* '''Pivotal role of the transcriptional co-activator YAP in trophoblast stemness of the developing human placenta''' [https://www.pnas.org/content/117/24/13562.abstract?etoc PMAS] "Defects in development and differentiation of the placenta are associated with various pregnancy disorders such as miscarriage, stillbirth, preeclampsia, and intrauterine growth restriction. However, our knowledge on critical regulators of human placentation is scarce. In the present study, we show that the Hippo signaling-dependent transcriptional coactivator YAP plays a pivotal role in the maintenance of proliferative trophoblasts, the epithelial cells of the placenta. By binding to the transcription factor TEAD4, YAP stimulates expression of genes promoting trophoblast stemness. Additionally, YAP–TEAD4 complexes actively repress genes associated with the differentiated syncytiotrophoblast, the hormone-secreting cell type of the human placenta. Hence, YAP orchestrates a complex developmental program ensuring growth and expansion of the human placenta. we herein show that YAP, the transcriptional coactivator of the Hippo signaling pathway, promotes maintenance of cytotrophoblast progenitors by different genomic mechanisms. Genetic or chemical manipulation of YAP in these cellular models revealed that it stimulates proliferation and expression of cell cycle regulators and stemness-associated genes, but inhibits cell fusion and production of syncytiotrophoblast (STB)-specific proteins, such as hCG and GDF15."

	* '''Cyclin-Dependent Kinase 7 [https://www.omim.org/entry/601955 CDK7] regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus'''{{#pmid:31857346\|PMID31857346}} "Hippo signaling controls organ size and tumor progression through a conserved pathway leading to nuclear translocation of the transcriptional effector Yki/Yap/Taz. Most of our understanding of Hippo signaling pertains to its cytoplasmic regulation, but how the pathway is controlled in the nucleus remains poorly understood. Here we uncover an evolutionarily conserved mechanism by which CDK7 promotes Yki/Yap/Taz stabilization in the nucleus to sustain Hippo pathway outputs. We found that a modular E3 ubiquitin ligase complex CRL4DCAF12 binds and targets Yki/Yap/Taz for ubiquitination and degradation, whereas CDK7 phosphorylates Yki/Yap/Taz at S169/S128/S90 to inhibit CRL4DCAF12 recruitment, leading to Yki/Yap/Taz stabilization. As a consequence, inactivation of CDK7 reduced organ size and inhibited tumor growth, which could be reversed by restoring Yki/Yap activity. Our study identifies an unanticipated layer of Hippo pathway regulation, defines a novel mechanism by which CDK7 regulates tissue growth, and implies CDK7 as a drug target for Yap/Taz-driven cancer." [https://www.omim.org/entry/601955 OMIM - CDK7]		* '''Cyclin-Dependent Kinase 7 [https://www.omim.org/entry/601955 CDK7] regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus'''{{#pmid:31857346\|PMID31857346}} "Hippo signaling controls organ size and tumor progression through a conserved pathway leading to nuclear translocation of the transcriptional effector Yki/Yap/Taz. Most of our understanding of Hippo signaling pertains to its cytoplasmic regulation, but how the pathway is controlled in the nucleus remains poorly understood. Here we uncover an evolutionarily conserved mechanism by which CDK7 promotes Yki/Yap/Taz stabilization in the nucleus to sustain Hippo pathway outputs. We found that a modular E3 ubiquitin ligase complex CRL4DCAF12 binds and targets Yki/Yap/Taz for ubiquitination and degradation, whereas CDK7 phosphorylates Yki/Yap/Taz at S169/S128/S90 to inhibit CRL4DCAF12 recruitment, leading to Yki/Yap/Taz stabilization. As a consequence, inactivation of CDK7 reduced organ size and inhibited tumor growth, which could be reversed by restoring Yki/Yap activity. Our study identifies an unanticipated layer of Hippo pathway regulation, defines a novel mechanism by which CDK7 regulates tissue growth, and implies CDK7 as a drug target for Yap/Taz-driven cancer." [https://www.omim.org/entry/601955 OMIM - CDK7]

Z8600021 at 22:35, 26 March 2020

2020-03-26T22:35:04Z

← Older revision		Revision as of 09:35, 27 March 2020
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	\| [[File:Mark_Hill.jpg\|90px\|left]] {{Most_Recent_Refs}}		\| [[File:Mark_Hill.jpg\|90px\|left]] {{Most_Recent_Refs}}

	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Embryo+Hippo ''Embryo Hippo''] \| [http://www.ncbi.nlm.nih.gov/pmc/?term=Hippo&report=imagesdocsum ''Images'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Embryo+Hippo ''Embryo Hippo''] \| [http://www.ncbi.nlm.nih.gov/pmc/?term=Hippo&report=imagesdocsum ''Images''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Embryo+YAP ''Embryo YAP''] \|
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
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	\| {{Older papers}}		\| {{Older papers}}

	* '''YAP is essential for tissue tension to ensure vertebrate 3D body shape'''{{#pmid:25778702\|PMID25778702}} "Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape." [[Medaka Development]]		* '''{{YAP}} is essential for tissue tension to ensure vertebrate 3D body shape'''{{#pmid:25778702\|PMID25778702}} "Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape." [[Medaka Development]]
	\|}		\|}

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	:'''Links:''' ~~[[Musculoskeletal System -~~ Bone ~~Development\|Bone Development]]~~		:'''Links:''' {{Bone}}

			==Neural==

			During early neural development {{radial glia}} guide the migration of differentiating neural cells to the developing cortical plate ({{cortex}}). A study has shown that elimination of CEP83, in radial glial progenitor cells, activates the mechanically sensitive yes-associated protein (YAP) and promotes the excessive proliferation of these progenitor cells.

			:'''Links:''' {{radial glia}} \| {{cortex}}
	==References==		==References==
	<references/>		<references/>

Z8600021 at 22:11, 7 Ocak 2020

2020-01-07T22:11:55Z

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			* '''Cyclin-Dependent Kinase 7 [https://www.omim.org/entry/601955 CDK7] regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus'''{{#pmid:31857346\|PMID31857346}} "Hippo signaling controls organ size and tumor progression through a conserved pathway leading to nuclear translocation of the transcriptional effector Yki/Yap/Taz. Most of our understanding of Hippo signaling pertains to its cytoplasmic regulation, but how the pathway is controlled in the nucleus remains poorly understood. Here we uncover an evolutionarily conserved mechanism by which CDK7 promotes Yki/Yap/Taz stabilization in the nucleus to sustain Hippo pathway outputs. We found that a modular E3 ubiquitin ligase complex CRL4DCAF12 binds and targets Yki/Yap/Taz for ubiquitination and degradation, whereas CDK7 phosphorylates Yki/Yap/Taz at S169/S128/S90 to inhibit CRL4DCAF12 recruitment, leading to Yki/Yap/Taz stabilization. As a consequence, inactivation of CDK7 reduced organ size and inhibited tumor growth, which could be reversed by restoring Yki/Yap activity. Our study identifies an unanticipated layer of Hippo pathway regulation, defines a novel mechanism by which CDK7 regulates tissue growth, and implies CDK7 as a drug target for Yap/Taz-driven cancer." [https://www.omim.org/entry/601955 OMIM - CDK7]

	* '''Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse'''{{#pmid:26902285\|PMID26902285}} "In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture."		* '''Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse'''{{#pmid:26902285\|PMID26902285}} "In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture."

	* '''Review - Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos'''{{#pmid:25986053\|PMID25986053}} "During the preimplantation stage, mouse embryos establish two cell lineages by the time of early blastocyst formation: the trophectoderm (TE) and the inner cell mass (ICM). Historical models have proposed that the establishment of these two lineages depends on the cell position within the embryo (e.g., the positional model) or cell polarization along the apicobasal axis (e.g., the polarity model). Recent findings have revealed that the Hippo signaling pathway plays a central role in the cell fate-specification process: active and inactive Hippo signaling in the inner and outer cells promote ICM and TE fates, respectively. Intercellular adhesion activates, while apicobasal polarization suppresses Hippo signaling, and a combination of these processes determines the spatially regulated activation of the Hippo pathway in 32-cell-stage embryos. Therefore, there is experimental evidence in favor of both positional and polarity models. At the molecular level, phosphorylation of the Hippo-pathway component angiomotin at adherens junctions (AJs) in the inner (apolar) cells activates the Lats protein kinase and triggers Hippo signaling. In the outer cells, however, cell polarization sequesters Amot from basolateral AJs and suppresses activation of the Hippo pathway. Other mechanisms, including asymmetric cell division and Notch signaling, also play important roles in the regulation of embryonic development. In this review, I discuss how these mechanisms cooperate with the Hippo signaling pathway during cell fate-specification processes." [[Developmental Signals - Notch]] \| [[Mouse Development]]		* '''Review - Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos'''{{#pmid:25986053\|PMID25986053}} "During the preimplantation stage, mouse embryos establish two cell lineages by the time of early blastocyst formation: the trophectoderm (TE) and the inner cell mass (ICM). Historical models have proposed that the establishment of these two lineages depends on the cell position within the embryo (e.g., the positional model) or cell polarization along the apicobasal axis (e.g., the polarity model). Recent findings have revealed that the Hippo signaling pathway plays a central role in the cell fate-specification process: active and inactive Hippo signaling in the inner and outer cells promote ICM and TE fates, respectively. Intercellular adhesion activates, while apicobasal polarization suppresses Hippo signaling, and a combination of these processes determines the spatially regulated activation of the Hippo pathway in 32-cell-stage embryos. Therefore, there is experimental evidence in favor of both positional and polarity models. At the molecular level, phosphorylation of the Hippo-pathway component angiomotin at adherens junctions (AJs) in the inner (apolar) cells activates the Lats protein kinase and triggers Hippo signaling. In the outer cells, however, cell polarization sequesters Amot from basolateral AJs and suppresses activation of the Hippo pathway. Other mechanisms, including asymmetric cell division and Notch signaling, also play important roles in the regulation of embryonic development. In this review, I discuss how these mechanisms cooperate with the Hippo signaling pathway during cell fate-specification processes." [[Developmental Signals - Notch]] \| [[Mouse Development]]

	* '''YAP is essential for tissue tension to ensure vertebrate 3D body shape'''{{#pmid:25778702\|PMID25778702}} "Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape." [[Medaka Development]]
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
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	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Embryo+Hippo ''Embryo Hippo''] \| [http://www.ncbi.nlm.nih.gov/pmc/?term=Hippo&report=imagesdocsum ''Images'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Embryo+Hippo ''Embryo Hippo''] \| [http://www.ncbi.nlm.nih.gov/pmc/?term=Hippo&report=imagesdocsum ''Images'']
			\|}
			{\| class="wikitable mw-collapsible mw-collapsed"
			! Older papers
			\|-
			\| {{Older papers}}

	~~<pubmed limit=5>Embryo~~ Hippo~~</pubmed>~~		* '''YAP is essential for tissue tension to ensure vertebrate 3D body shape'''{{#pmid:25778702\|PMID25778702}} "Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape." [[Medaka Development]]
	\|}		\|}

Z8600021 at 23:14, 20 March 2018

2018-03-20T23:14:09Z

← Older revision		Revision as of 10:14, 21 March 2018
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	Hippo is a protein kinase cascade pathway, getting its name from the “hippopotamus”-like fly phenotype.		Hippo is a protein kinase cascade pathway, getting its name from the “hippopotamus”-like fly phenotype.



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	==Early Development==		==Early Development==

	==Zygote==		===Zygote===

	Maternally inherited Yes-associated protein (Yap), a co-activator of TEAD family transcription factors, plays a key role in activating embryonic transcription following fertilization in the mouse. Lysophosphatidic acid (LPA) in the mouse tubal fluid binds to its G-protein coupled receptor at the plasma membrane, and induces the activation of YAP by inhibiting LATS1/2. {{#pmid:26902285\|PMID26902285}}		Maternally inherited Yes-associated protein (Yap), a co-activator of TEAD family transcription factors, plays a key role in activating embryonic transcription following fertilization in the mouse. Lysophosphatidic acid (LPA) in the mouse tubal fluid binds to its G-protein coupled receptor at the plasma membrane, and induces the activation of YAP by inhibiting LATS1/2. {{#pmid:26902285\|PMID26902285}}
Line 54:		Line 53:

	===Blastocyst===		===Blastocyst===
			Current research suggests that this signaling pathways is involved with the first "patterning" decision cells make in the [[Blastocyst\|blastocyst]], controlling trophectoderm vs inner cell mass decision making.


	{{Blastocyst Hippo table}}		{{Blastocyst Hippo table}}

Z8600021 at 23:12, 20 March 2018

2018-03-20T23:12:39Z

@@ Line 54: / Line 54: @@
 ===Blastocyst===
-:(Table data see review{{#pmid:25986053|PMID25986053}} Notch signaling also has a role in blastocyst fate development)
+{{Blastocyst Hippo table}}
 :'''Links:''' [[Blastocyst]]

Z8600021 at 23:11, 20 March 2018

2018-03-20T23:11:29Z

← Older revision		Revision as of 10:11, 21 March 2018
Line 5:		Line 5:

	Hippo is a protein kinase cascade pathway, getting its name from the “hippopotamus”-like fly phenotype.		Hippo is a protein kinase cascade pathway, getting its name from the “hippopotamus”-like fly phenotype.



			Current research suggests that this signaling pathways is involved with the first "patterning" decision cells make in the [[Blastocyst\|blastocyst]], controlling trophectoderm vs inner cell mass decision making.

	{\|		{\|