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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, A J; Brivanlou, Ali H.
Afiliación
  • Piccolo FM; Laboratory of of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, United States.
  • Kastan NR; Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
  • Haremaki T; Laboratory of Sensory Neuroscience, The Rockefeller University, New York, United States.
  • Tian Q; Laboratory of of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, United States.
  • Laundos TL; Laboratory of of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, United States.
  • De Santis R; Laboratory of of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, United States.
  • Beaudoin AJ; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
  • Carroll TS; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • Luo JD; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
  • Gnedeva K; Laboratory of of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, United States.
  • Etoc F; Laboratory of of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, United States.
  • Hudspeth AJ; Bioinformatics Resource Center, The Rockefeller University, New York, United States.
  • Brivanlou AH; Bioinformatics Resource Center, The Rockefeller University, New York, United States.
Elife ; 112022 04 22.
Article en En | MEDLINE | ID: mdl-35451959
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / Ectodermo / Proteínas Señalizadoras YAP Límite: Humans Idioma: En Revista: Elife Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / Ectodermo / Proteínas Señalizadoras YAP Límite: Humans Idioma: En Revista: Elife Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido