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Molecular Evolution of the Yap/Yorkie Proto-Oncogene and Elucidation of Its Core Transcriptional Program
Throughout Metazoa, developmental processes are controlled by a surprisingly limited number of conserved signaling pathways. Precisely how these signaling cassettes were assembled in early animal evolution remains poorly understood, as do the molecular transitions that potentiated the acquisition of...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032125/ https://www.ncbi.nlm.nih.gov/pubmed/24509725 http://dx.doi.org/10.1093/molbev/msu071 |
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author | Ikmi, Aissam Gaertner, Bjoern Seidel, Christopher Srivastava, Mansi Zeitlinger, Julia Gibson, Matthew C. |
author_facet | Ikmi, Aissam Gaertner, Bjoern Seidel, Christopher Srivastava, Mansi Zeitlinger, Julia Gibson, Matthew C. |
author_sort | Ikmi, Aissam |
collection | PubMed |
description | Throughout Metazoa, developmental processes are controlled by a surprisingly limited number of conserved signaling pathways. Precisely how these signaling cassettes were assembled in early animal evolution remains poorly understood, as do the molecular transitions that potentiated the acquisition of their myriad developmental functions. Here we analyze the molecular evolution of the proto-oncogene yes-associated protein (Yap)/Yorkie, a key effector of the Hippo signaling pathway that controls organ size in both Drosophila and mammals. Based on heterologous functional analysis of evolutionarily distant Yap/Yorkie orthologs, we demonstrate that a structurally distinct interaction interface between Yap/Yorkie and its partner TEAD/Scalloped became fixed in the eumetazoan common ancestor. We then combine transcriptional profiling of tissues expressing phylogenetically diverse forms of Yap/Yorkie with ChIP-seq validation to identify a common downstream gene expression program underlying the control of tissue growth in Drosophila. Intriguingly, a subset of the newly identified Yorkie target genes are also induced by Yap in mammalian tissues, thus revealing a conserved Yap-dependent gene expression signature likely to mediate organ size control throughout bilaterian animals. Combined, these experiments provide new mechanistic insights while revealing the ancient evolutionary history of Hippo signaling. |
format | Online Article Text |
id | pubmed-4032125 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40321252014-06-18 Molecular Evolution of the Yap/Yorkie Proto-Oncogene and Elucidation of Its Core Transcriptional Program Ikmi, Aissam Gaertner, Bjoern Seidel, Christopher Srivastava, Mansi Zeitlinger, Julia Gibson, Matthew C. Mol Biol Evol Discoveries Throughout Metazoa, developmental processes are controlled by a surprisingly limited number of conserved signaling pathways. Precisely how these signaling cassettes were assembled in early animal evolution remains poorly understood, as do the molecular transitions that potentiated the acquisition of their myriad developmental functions. Here we analyze the molecular evolution of the proto-oncogene yes-associated protein (Yap)/Yorkie, a key effector of the Hippo signaling pathway that controls organ size in both Drosophila and mammals. Based on heterologous functional analysis of evolutionarily distant Yap/Yorkie orthologs, we demonstrate that a structurally distinct interaction interface between Yap/Yorkie and its partner TEAD/Scalloped became fixed in the eumetazoan common ancestor. We then combine transcriptional profiling of tissues expressing phylogenetically diverse forms of Yap/Yorkie with ChIP-seq validation to identify a common downstream gene expression program underlying the control of tissue growth in Drosophila. Intriguingly, a subset of the newly identified Yorkie target genes are also induced by Yap in mammalian tissues, thus revealing a conserved Yap-dependent gene expression signature likely to mediate organ size control throughout bilaterian animals. Combined, these experiments provide new mechanistic insights while revealing the ancient evolutionary history of Hippo signaling. Oxford University Press 2014-06 2014-02-08 /pmc/articles/PMC4032125/ /pubmed/24509725 http://dx.doi.org/10.1093/molbev/msu071 Text en © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Discoveries Ikmi, Aissam Gaertner, Bjoern Seidel, Christopher Srivastava, Mansi Zeitlinger, Julia Gibson, Matthew C. Molecular Evolution of the Yap/Yorkie Proto-Oncogene and Elucidation of Its Core Transcriptional Program |
title | Molecular Evolution of the Yap/Yorkie Proto-Oncogene and Elucidation of Its Core Transcriptional Program |
title_full | Molecular Evolution of the Yap/Yorkie Proto-Oncogene and Elucidation of Its Core Transcriptional Program |
title_fullStr | Molecular Evolution of the Yap/Yorkie Proto-Oncogene and Elucidation of Its Core Transcriptional Program |
title_full_unstemmed | Molecular Evolution of the Yap/Yorkie Proto-Oncogene and Elucidation of Its Core Transcriptional Program |
title_short | Molecular Evolution of the Yap/Yorkie Proto-Oncogene and Elucidation of Its Core Transcriptional Program |
title_sort | molecular evolution of the yap/yorkie proto-oncogene and elucidation of its core transcriptional program |
topic | Discoveries |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032125/ https://www.ncbi.nlm.nih.gov/pubmed/24509725 http://dx.doi.org/10.1093/molbev/msu071 |
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