Developmental Signals - Hippo: Difference between revisions
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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''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Embryo+YAP ''Embryo YAP''] | | ||
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* '''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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==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/> |
Revision as of 08:35, 27 March 2020
Embryology - 20 Jun 2024 Expand to Translate |
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Introduction
The Hippo (Hpo) pathway, first identified in Drosophila, controls organ size by regulating cell proliferation (inhibition) and apoptosis (induction). In contrast, the TOR signalling pathway regulates organ size by stimulating cell growth, thus increasing cell size.
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, controlling trophectoderm vs inner cell mass decision making.
Fly Phenotype (dorsal view head thorax SEM) | |
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Hippo-type (hpo) | Wild-type (WT) |
Image source[1] |
Factor Links: AMH | hCG | BMP | sonic hedgehog | bHLH | HOX | FGF | FOX | Hippo | LIM | Nanog | NGF | Nodal | Notch | PAX | retinoic acid | SIX | Slit2/Robo1 | SOX | TBX | TGF-beta | VEGF | WNT | Category:Molecular |
Some Recent Findings
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More recent papers |
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Embryo Hippo | Images | Embryo YAP | |
Older papers |
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These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.
See also the Discussion Page for other references listed by year and References on this current page.
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Early Development
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. [3]
- Links: Zygote | Mouse Development
Blastocyst
Current research suggests that this signaling pathways is involved with the first "patterning" decision cells make in the blastocyst, controlling trophectoderm vs inner cell mass decision making.
Mouse Blastocyst (32 cell stage) Fate | |
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Inner cells | Outer cells |
Angiomotin (Amot) phosphorylation at adherens junctions | Amot sequestered by cell polarization from basolateral adherens junctions |
Hippo active | Hippo inactive |
Notch inactive | Notch active |
Cdx2 not expressed | Cdx2 expressed |
ICM - inner cell mass fate | TE - trophectoderm fate |
Hippo[4](TEAD4) and Notch[6](Cdx2) together appear regulate early blastocyst fate development. |
- Links: Blastocyst
Bone
Hippo signaling pathway has recently been identified as a key regulator of osteoclast formation, see review.[7]
- Hippo signaling pathway regulatory molecules - RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP, and TAZ.
- osteoclast differentiation - upon activation, MST and LAST, transcriptional co-activators YAP and TAZ bind to the members of the TEA domain (TEAD) family transcription factors
- regulate expression of downstream target genes connective tissue growth factor (CTGF/CCN2) and cysteine-rich protein 61 (CYR61/CCN1).
- RANKL-mediated signaling cascades including NF-κB, MAPKs, AP1, and NFATc1, Hippo-signaling molecules such as YAP/TAZ/TEAD complex, RASSF2, MST2, and Ajuba could also potentially modulate osteoclast differentiation and function.
- 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
- ↑ 1.0 1.1 Johnson R & Halder G. (2014). The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov , 13, 63-79. PMID: 24336504 DOI.
- ↑ Cho YS, Li S, Wang X, Zhu J, Zhuo S, Han Y, Yue T, Yang Y & Jiang J. (2020). CDK7 regulates organ size and tumor growth by safeguarding the Hippo pathway effector Yki/Yap/Taz in the nucleus. Genes Dev. , 34, 53-71. PMID: 31857346 DOI.
- ↑ 3.0 3.1 Yu C, Ji SY, Dang YJ, Sha QQ, Yuan YF, Zhou JJ, Yan LY, Qiao J, Tang F & Fan HY. (2016). Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse. Cell Res. , 26, 275-87. PMID: 26902285 DOI.
- ↑ 4.0 4.1 Sasaki H. (2015). Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos. Semin. Cell Dev. Biol. , 47-48, 80-7. PMID: 25986053 DOI.
- ↑ Porazinski S, Wang H, Asaoka Y, Behrndt M, Miyamoto T, Morita H, Hata S, Sasaki T, Krens SFG, Osada Y, Asaka S, Momoi A, Linton S, Miesfeld JB, Link BA, Senga T, Shimizu N, Nagase H, Matsuura S, Bagby S, Kondoh H, Nishina H, Heisenberg CP & Furutani-Seiki M. (2015). YAP is essential for tissue tension to ensure vertebrate 3D body shape. Nature , 521, 217-221. PMID: 25778702 DOI.
- ↑ Rayon T, Menchero S, Nieto A, Xenopoulos P, Crespo M, Cockburn K, Cañon S, Sasaki H, Hadjantonakis AK, de la Pompa JL, Rossant J & Manzanares M. (2014). Notch and hippo converge on Cdx2 to specify the trophectoderm lineage in the mouse blastocyst. Dev. Cell , 30, 410-22. PMID: 25127056 DOI.
- ↑ Yang W, Han W, Qin A, Wang Z, Xu J & Qian Y. (2018). The emerging role of Hippo signaling pathway in regulating osteoclast formation. J. Cell. Physiol. , 233, 4606-4617. PMID: 29219182 DOI.
Reviews
Irvine KD & Harvey KF. (2015). Control of organ growth by patterning and hippo signaling in Drosophila. Cold Spring Harb Perspect Biol , 7, . PMID: 26032720 DOI.
Tumaneng K, Russell RC & Guan KL. (2012). Organ size control by Hippo and TOR pathways. Curr. Biol. , 22, R368-79. PMID: 22575479 DOI.
Zhao B, Tumaneng K & Guan KL. (2011). The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat. Cell Biol. , 13, 877-83. PMID: 21808241 DOI.
Kango-Singh M & Singh A. (2009). Regulation of organ size: insights from the Drosophila Hippo signaling pathway. Dev. Dyn. , 238, 1627-37. PMID: 19517570 DOI.
Articles
Bessonnard S, Mesnard D & Constam DB. (2015). PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation. J. Cell Biol. , 210, 1185-97. PMID: 26416966 DOI.
Yuan H, Liu H, Liu Z, Zhu D, Amos CI, Fang S, Lee JE & Wei Q. (2015). Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival. Int. J. Cancer , 137, 638-45. PMID: 25628125 DOI.
Clattenburg L, Wigerius M, Qi J, Rainey JK, Rourke JL, Muruganandan S, Sinal CJ & Fawcett JP. (2015). NOS1AP Functionally Associates with YAP To Regulate Hippo Signaling. Mol. Cell. Biol. , 35, 2265-77. PMID: 25918243 DOI.
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Cite this page: Hill, M.A. (2024, June 20) Embryology Developmental Signals - Hippo. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Hippo
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G