TY - JOUR
T1 - Premetazoan Origin of the Hippo Signaling Pathway
AU - Sebe-Pedrs, Arnau
AU - Zheng, Yonggang
AU - Ruiz-Trillo, Iñaki
AU - Pan, Duojia
N1 - Funding Information:
The genome sequences of C. owczarzaki, S. rosetta, A. macrogynus, S. punctatus, and T. trahens are being determined by the Broad Institute of MIT/Harvard University under the auspices of the National Human Genome Research Institute (NHGRI) and within the UNICORN initiative. We thank Joint Genome Institute, Broad Institute, and Baylor College of Medicine for making data publicly available. We also thank Dr. Kim Worley and her colleagues in the Human Genome Sequencing Center of Baylor College of Medicine for allowing us to use the A. castellanii genome sequence. We are grateful to Drs. Rick Fehon and Bruce Hay for providing antibodies used in this study. This work was supported by an Institució Catalana per a la Recerca i Estudis Avançats contract, a European Research Council Starting Grant (ERC-2007-StG-206883), a grant (BFU2008-02839/BMC) from Ministerio de Ciencia e Innovación (MICINN) to I. R.-T., and a National Institutes of Health grant (R01 EY015708) to D.P. A.S-P. was supported by a pregraduate Formacion Profesorado Universitario grant from MICINN. D.P. is an investigator of the Howard Hughes Medical Institute.
PY - 2012/1/26
Y1 - 2012/1/26
N2 - Nonaggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of the Hippo pathway in nonbilaterian animals, but failed to identify this pathway outside Metazoa. Through comparative analyses of recently sequenced holozoan genomes, we show that Hippo pathway components, such as the kinases Hippo and Warts, the coactivator Yorkie, and the transcription factor Scalloped, were already present in the unicellular ancestors of animals. Remarkably, functional analysis of Hippo components of the amoeboid holozoan Capsaspora owczarzaki, performed in Drosophila melanogaster, demonstrate that the growth-regulatory activity of the Hippo pathway is conserved in this unicellular lineage. Our findings show that the Hippo pathway evolved well before the origin of Metazoa and highlight the importance of Hippo signaling as a key developmental mechanism predating the origin of Metazoa.
AB - Nonaggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of the Hippo pathway in nonbilaterian animals, but failed to identify this pathway outside Metazoa. Through comparative analyses of recently sequenced holozoan genomes, we show that Hippo pathway components, such as the kinases Hippo and Warts, the coactivator Yorkie, and the transcription factor Scalloped, were already present in the unicellular ancestors of animals. Remarkably, functional analysis of Hippo components of the amoeboid holozoan Capsaspora owczarzaki, performed in Drosophila melanogaster, demonstrate that the growth-regulatory activity of the Hippo pathway is conserved in this unicellular lineage. Our findings show that the Hippo pathway evolved well before the origin of Metazoa and highlight the importance of Hippo signaling as a key developmental mechanism predating the origin of Metazoa.
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U2 - 10.1016/j.celrep.2011.11.004
DO - 10.1016/j.celrep.2011.11.004
M3 - Article
C2 - 22832104
AN - SCOPUS:84857129984
SN - 2211-1247
VL - 1
SP - 13
EP - 20
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -