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Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation

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...

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Autores principales: Piccolo, Francesco M, Kastan, Nathaniel R, Haremaki, Tomomi, Tian, Qingyun, Laundos, Tiago L, De Santis, Riccardo, Beaudoin, Andrew J, Carroll, Thomas S, Luo, Ji-Dung, Gnedeva, Ksenia, Etoc, Fred, Hudspeth, AJ, Brivanlou, Ali H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033270/
https://www.ncbi.nlm.nih.gov/pubmed/35451959
http://dx.doi.org/10.7554/eLife.73075
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author Piccolo, Francesco M
Kastan, Nathaniel R
Haremaki, Tomomi
Tian, Qingyun
Laundos, Tiago L
De Santis, Riccardo
Beaudoin, Andrew J
Carroll, Thomas S
Luo, Ji-Dung
Gnedeva, Ksenia
Etoc, Fred
Hudspeth, AJ
Brivanlou, Ali H
author_facet Piccolo, Francesco M
Kastan, Nathaniel R
Haremaki, Tomomi
Tian, Qingyun
Laundos, Tiago L
De Santis, Riccardo
Beaudoin, Andrew J
Carroll, Thomas S
Luo, Ji-Dung
Gnedeva, Ksenia
Etoc, Fred
Hudspeth, AJ
Brivanlou, Ali H
author_sort Piccolo, Francesco M
collection PubMed
description 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.
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spelling pubmed-90332702022-04-23 Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation Piccolo, Francesco M Kastan, Nathaniel R Haremaki, Tomomi Tian, Qingyun Laundos, Tiago L De Santis, Riccardo Beaudoin, Andrew J Carroll, Thomas S Luo, Ji-Dung Gnedeva, Ksenia Etoc, Fred Hudspeth, AJ Brivanlou, Ali H eLife Cell Biology 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. eLife Sciences Publications, Ltd 2022-04-22 /pmc/articles/PMC9033270/ /pubmed/35451959 http://dx.doi.org/10.7554/eLife.73075 Text en © 2022, Piccolo et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Piccolo, Francesco M
Kastan, Nathaniel R
Haremaki, Tomomi
Tian, Qingyun
Laundos, Tiago L
De Santis, Riccardo
Beaudoin, Andrew J
Carroll, Thomas S
Luo, Ji-Dung
Gnedeva, Ksenia
Etoc, Fred
Hudspeth, AJ
Brivanlou, Ali H
Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation
title Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation
title_full Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation
title_fullStr Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation
title_full_unstemmed Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation
title_short Role of YAP in early ectodermal specification and a Huntington's Disease model of human neurulation
title_sort role of yap in early ectodermal specification and a huntington's disease model of human neurulation
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033270/
https://www.ncbi.nlm.nih.gov/pubmed/35451959
http://dx.doi.org/10.7554/eLife.73075
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