{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:25:23Z","timestamp":1790792723254,"version":"4.1.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T00:00:00Z","timestamp":1562284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T00:00:00Z","timestamp":1562284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100016944","name":"Regenerative Medicine Minnesota","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016944","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Etv2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. While the transcriptional networks during hemato-endothelial development have been well described, the mechanistic details are incompletely defined. In the present study, we described a new role for Etv2 as a regulator of cellular proliferation via <jats:italic>Yes1<\/jats:italic> in mesodermal lineages. Analysis of an Etv2-ChIPseq dataset revealed significant enrichment of Etv2 peaks in the upstream regions of cell cycle regulatory genes relative to non-cell cycle genes. Our bulk-RNAseq analysis using the doxycycline-inducible Etv2 ES\/EB system showed increased levels of cell cycle genes including <jats:italic>E<\/jats:italic>2<jats:italic>f4<\/jats:italic> and <jats:italic>Ccne1<\/jats:italic> as early as 6\u2009h following Etv2 induction. Further, EdU-incorporation studies demonstrated that the induction of Etv2 resulted in a ~2.5-fold increase in cellular proliferation, supporting a proliferative role for Etv2 during differentiation. Next, we identified <jats:italic>Yes1<\/jats:italic> as the top-ranked candidate that was expressed in <jats:italic>Etv2<\/jats:italic>-<jats:italic>EYFP<\/jats:italic><jats:sup>+<\/jats:sup> cells at E7.75 and E8.25 using single cell RNA-seq analysis. Doxycycline-mediated induction of Etv2 led to an increase in <jats:italic>Yes1<\/jats:italic> transcripts in a dose-dependent fashion. In contrast, the level of <jats:italic>Yes1<\/jats:italic> was reduced in <jats:italic>Etv2 null<\/jats:italic> embryoid bodies. Using bioinformatics algorithms, biochemical, and molecular biology techniques, we show that Etv2 binds to the promoter region of <jats:italic>Yes1<\/jats:italic> and functions as a direct upstream transcriptional regulator of <jats:italic>Yes1<\/jats:italic> during embryogenesis. These studies enhance our understanding of the mechanisms whereby Etv2 governs mesodermal fate decisions early during embryogenesis.<\/jats:p>","DOI":"10.1038\/s41598-019-45841-5","type":"journal-article","created":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T10:03:06Z","timestamp":1562320986000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis"],"prefix":"10.1038","volume":"9","author":[{"given":"Bhairab N.","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3147-4028","authenticated-orcid":false,"given":"Wuming","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyabrata","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua W. M.","family":"Theisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier E.","family":"Sierra-Pagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetris","family":"Yannopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Skie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pruthvi","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary G.","family":"Garry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Garry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,5]]},"reference":[{"key":"45841_CR1","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.celrep.2015.09.060","volume":"13","author":"BN Singh","year":"2015","unstructured":"Singh, B. N. et al. The Etv2-miR-130a Network Regulates Mesodermal Specification. Cell Rep 13, 915\u2013923, https:\/\/doi.org\/10.1016\/j.celrep.2015.09.060 (2015).","journal-title":"Cell Rep"},{"key":"45841_CR2","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1073\/pnas.0807583106","volume":"106","author":"A Ferdous","year":"2009","unstructured":"Ferdous, A. et al. Nkx2-5 transactivates the Ets-related protein 71 gene and specifies an endothelial\/endocardial fate in the developing embryo. Proc Natl Acad Sci USA 106, 814\u2013819, https:\/\/doi.org\/10.1073\/pnas.0807583106 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"45841_CR3","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s10456-017-9539-8","volume":"20","author":"K Baltrunaite","year":"2017","unstructured":"Baltrunaite, K. et al. ETS transcription factors Etv2 and Fli1b are required for tumor angiogenesis. Angiogenesis 20, 307\u2013323, https:\/\/doi.org\/10.1007\/s10456-017-9539-8 (2017).","journal-title":"Angiogenesis"},{"key":"45841_CR4","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ydbio.2018.05.003","volume":"440","author":"JA Davis","year":"2018","unstructured":"Davis, J. A. et al. ETS transcription factor Etsrp \/ Etv2 is required for lymphangiogenesis and directly regulates vegfr3 \/ flt4 expression. Dev Biol 440, 40\u201352, https:\/\/doi.org\/10.1016\/j.ydbio.2018.05.003 (2018).","journal-title":"Dev Biol"},{"key":"45841_CR5","doi-asserted-by":"publisher","first-page":"4801","DOI":"10.1242\/dev.070912","volume":"138","author":"TL Rasmussen","year":"2011","unstructured":"Rasmussen, T. L. et al. ER71 directs mesodermal fate decisions during embryogenesis. Development 138, 4801\u20134812, https:\/\/doi.org\/10.1242\/dev.070912 (2011).","journal-title":"Development"},{"key":"45841_CR6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.stem.2008.03.008","volume":"2","author":"D Lee","year":"2008","unstructured":"Lee, D. et al. ER71 acts downstream of BMP, Notch, and Wnt signaling in blood and vessel progenitor specification. Cell Stem Cell 2, 497\u2013507, https:\/\/doi.org\/10.1016\/j.stem.2008.03.008 (2008).","journal-title":"Cell Stem Cell"},{"key":"45841_CR7","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1161\/ATVBAHA.114.304768","volume":"35","author":"MP Craig","year":"2015","unstructured":"Craig, M. P. et al. Etv2 and fli1b function together as key regulators of vasculogenesis and angiogenesis. Arterioscler Thromb Vasc Biol 35, 865\u2013876, https:\/\/doi.org\/10.1161\/ATVBAHA.114.304768 (2015).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"45841_CR8","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1002\/stem.1131","volume":"30","author":"N Koyano-Nakagawa","year":"2012","unstructured":"Koyano-Nakagawa, N. et al. Etv2 is expressed in the yolk sac hematopoietic and endothelial progenitors and regulates Lmo2 gene expression. Stem Cells 30, 1611\u20131623, https:\/\/doi.org\/10.1002\/stem.1131 (2012).","journal-title":"Stem Cells"},{"key":"45841_CR9","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/j.cell.2008.10.049","volume":"135","author":"S De Val","year":"2008","unstructured":"De Val, S. et al. Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors. Cell 135, 1053\u20131064, https:\/\/doi.org\/10.1016\/j.cell.2008.10.049 (2008).","journal-title":"Cell"},{"key":"45841_CR10","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.ydbio.2014.02.018","volume":"389","author":"X Shi","year":"2014","unstructured":"Shi, X. et al. Cooperative interaction of Etv2 and Gata2 regulates the development of endothelial and hematopoietic lineages. Dev Biol 389, 208\u2013218, https:\/\/doi.org\/10.1016\/j.ydbio.2014.02.018 (2014).","journal-title":"Dev Biol"},{"key":"45841_CR11","doi-asserted-by":"publisher","first-page":"28107","DOI":"10.1074\/jbc.M115.662197","volume":"290","author":"N Koyano-Nakagawa","year":"2015","unstructured":"Koyano-Nakagawa, N. et al. Feedback Mechanisms Regulate Ets Variant 2 (Etv2) Gene Expression and Hematoendothelial Lineages. J Biol Chem 290, 28107\u201328119, https:\/\/doi.org\/10.1074\/jbc.M115.662197 (2015).","journal-title":"J Biol Chem"},{"key":"45841_CR12","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1101\/gad.1536007","volume":"21","author":"D Pan","year":"2007","unstructured":"Pan, D. Hippo signaling in organ size control. Genes Dev 21, 886\u2013897, https:\/\/doi.org\/10.1101\/gad.1536007 (2007).","journal-title":"Genes Dev"},{"key":"45841_CR13","doi-asserted-by":"publisher","first-page":"68","DOI":"10.4161\/fly.3.1.7788","volume":"3","author":"L Zhang","year":"2009","unstructured":"Zhang, L., Yue, T. & Jiang, J. Hippo signaling pathway and organ size control. Fly (Austin) 3, 68\u201373 (2009).","journal-title":"Fly (Austin)"},{"key":"45841_CR14","first-page":"2145","volume":"9","author":"M Sudol","year":"1994","unstructured":"Sudol, M. Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene 9, 2145\u20132152 (1994).","journal-title":"Oncogene"},{"key":"45841_CR15","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1242\/dev.102376","volume":"141","author":"X Varelas","year":"2014","unstructured":"Varelas, X. The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 141, 1614\u20131626, https:\/\/doi.org\/10.1242\/dev.102376 (2014).","journal-title":"Development"},{"key":"45841_CR16","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1093\/emboj\/18.9.2459","volume":"18","author":"RA Klinghoffer","year":"1999","unstructured":"Klinghoffer, R. A., Sachsenmaier, C., Cooper, J. A. & Soriano, P. Src family kinases are required for integrin but not PDGFR signal transduction. EMBO J 18, 2459\u20132471, https:\/\/doi.org\/10.1093\/emboj\/18.9.2459 (1999).","journal-title":"EMBO J"},{"key":"45841_CR17","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1101\/gad.8.17.1999","volume":"8","author":"PL Stein","year":"1994","unstructured":"Stein, P. L., Vogel, H. & Soriano, P. Combined deficiencies of Src, Fyn, and Yes tyrosine kinases in mutant mice. Genes Dev 8, 1999\u20132007 (1994).","journal-title":"Genes Dev"},{"key":"45841_CR18","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.ydbio.2006.05.023","volume":"297","author":"AD Mori","year":"2006","unstructured":"Mori, A. D. et al. Tbx5-dependent rheostatic control of cardiac gene expression and morphogenesis. Dev Biol 297, 566\u2013586, https:\/\/doi.org\/10.1016\/j.ydbio.2006.05.023 (2006).","journal-title":"Dev Biol"},{"key":"45841_CR19","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/S0960-9822(94)00025-4","volume":"4","author":"F Kiefer","year":"1994","unstructured":"Kiefer, F. et al. Endothelial cell transformation by polyomavirus middle T antigen in mice lacking Src-related kinases. Curr Biol 4, 100\u2013109 (1994).","journal-title":"Curr Biol"},{"key":"45841_CR20","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1128\/MCB.26.1.77-87.2006","volume":"26","author":"EM Morin-Kensicki","year":"2006","unstructured":"Morin-Kensicki, E. M. et al. Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65. Mol Cell Biol 26, 77\u201387, https:\/\/doi.org\/10.1128\/MCB.26.1.77-87.2006 (2006).","journal-title":"Mol Cell Biol"},{"key":"45841_CR21","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.devcel.2008.01.006","volume":"14","author":"L Zhang","year":"2008","unstructured":"Zhang, L. et al. The TEAD\/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control. Dev Cell 14, 377\u2013387, https:\/\/doi.org\/10.1016\/j.devcel.2008.01.006 (2008).","journal-title":"Dev Cell"},{"key":"45841_CR22","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1016\/j.cell.2012.11.026","volume":"151","author":"J Rosenbluh","year":"2012","unstructured":"Rosenbluh, J. et al. beta-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis. Cell 151, 1457\u20131473, https:\/\/doi.org\/10.1016\/j.cell.2012.11.026 (2012).","journal-title":"Cell"},{"key":"45841_CR23","doi-asserted-by":"publisher","first-page":"6975","DOI":"10.1182\/blood-2011-05-352658","volume":"118","author":"H Kataoka","year":"2011","unstructured":"Kataoka, H. et al. Etv2\/ER71 induces vascular mesoderm from Flk1\u2009+\u2009PDGFRalpha\u2009+\u2009primitive mesoderm. Blood 118, 6975\u20136986, https:\/\/doi.org\/10.1182\/blood-2011-05-352658 (2011).","journal-title":"Blood"},{"key":"45841_CR24","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1002\/dvdy.22277","volume":"239","author":"MC Salanga","year":"2010","unstructured":"Salanga, M. C., Meadows, S. M., Myers, C. T. & Krieg, P. A. ETS family protein ETV2 is required for initiation of the endothelial lineage but not the hematopoietic lineage in the Xenopus embryo. Dev Dyn 239, 1178\u20131187, https:\/\/doi.org\/10.1002\/dvdy.22277 (2010).","journal-title":"Dev Dyn"},{"key":"45841_CR25","doi-asserted-by":"publisher","first-page":"654","DOI":"10.15252\/embr.201439939","volume":"16","author":"F Liu","year":"2015","unstructured":"Liu, F. et al. Induction of hematopoietic and endothelial cell program orchestrated by ETS transcription factor ER71\/ETV2. EMBO Rep 16, 654\u2013669, https:\/\/doi.org\/10.15252\/embr.201439939 (2015).","journal-title":"EMBO Rep"},{"key":"45841_CR26","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.3892\/or.2012.2010","volume":"28","author":"A Sato","year":"2012","unstructured":"Sato, A., Sekine, M., Virgona, N., Ota, M. & Yano, T. Yes is a central mediator of cell growth in malignant mesothelioma cells. Oncol Rep 28, 1889\u20131893, https:\/\/doi.org\/10.3892\/or.2012.2010 (2012).","journal-title":"Oncol Rep"},{"key":"45841_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14362","volume":"8","author":"W Gong","year":"2017","unstructured":"Gong, W. et al. Dpath software reveals hierarchical haemato-endothelial lineages of Etv2 progenitors based on single-cell transcriptome analysis. Nat Commun 8, 14362, https:\/\/doi.org\/10.1038\/ncomms14362 (2017).","journal-title":"Nat Commun"},{"key":"45841_CR28","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/nature07085","volume":"454","author":"JM Verheyden","year":"2008","unstructured":"Verheyden, J. M. & Sun, X. An Fgf\/Gremlin inhibitory feedback loop triggers termination of limb bud outgrowth. Nature 454, 638\u2013641, https:\/\/doi.org\/10.1038\/nature07085 (2008).","journal-title":"Nature"},{"key":"45841_CR29","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ydbio.2012.07.033","volume":"371","author":"BN Singh","year":"2012","unstructured":"Singh, B. N., Doyle, M. J., Weaver, C. V., Koyano-Nakagawa, N. & Garry, D. J. Hedgehog and Wnt coordinate signaling in myogenic progenitors and regulate limb regeneration. Dev Biol 371, 23\u201334, https:\/\/doi.org\/10.1016\/j.ydbio.2012.07.033 (2012).","journal-title":"Dev Biol"},{"key":"45841_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06617-z","volume":"9","author":"BN Singh","year":"2018","unstructured":"Singh, B. N. et al. A conserved HH-Gli1-Mycn network regulates heart regeneration from newt to human. Nat Commun 9, 4237, https:\/\/doi.org\/10.1038\/s41467-018-06617-z (2018).","journal-title":"Nat Commun"},{"key":"45841_CR31","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1073\/pnas.1311705111","volume":"111","author":"L Zhao","year":"2014","unstructured":"Zhao, L. et al. Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration. Proc Natl Acad Sci USA 111, 1403\u20131408, https:\/\/doi.org\/10.1073\/pnas.1311705111 (2014).","journal-title":"Proc Natl Acad Sci USA"},{"key":"45841_CR32","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.ydbio.2006.08.016","volume":"299","author":"A Smith","year":"2006","unstructured":"Smith, A., Avaron, F., Guay, D., Padhi, B. K. & Akimenko, M. A. Inhibition of BMP signaling during zebrafish fin regeneration disrupts fin growth and scleroblasts differentiation and function. Dev Biol 299, 438\u2013454, https:\/\/doi.org\/10.1016\/j.ydbio.2006.08.016 (2006).","journal-title":"Dev Biol"},{"key":"45841_CR33","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.stem.2014.10.003","volume":"15","author":"A Aguirre","year":"2014","unstructured":"Aguirre, A. et al. In vivo activation of a conserved microRNA program induces mammalian heart regeneration. Cell Stem Cell 15, 589\u2013604, https:\/\/doi.org\/10.1016\/j.stem.2014.10.003 (2014).","journal-title":"Cell Stem Cell"},{"key":"45841_CR34","doi-asserted-by":"publisher","first-page":"5173","DOI":"10.1242\/dev.02101","volume":"132","author":"Y Lee","year":"2005","unstructured":"Lee, Y., Grill, S., Sanchez, A., Murphy-Ryan, M. & Poss, K. D. Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration. Development 132, 5173\u20135183, https:\/\/doi.org\/10.1242\/dev.02101 (2005).","journal-title":"Development"},{"key":"45841_CR35","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.stem.2013.03.004","volume":"12","author":"SS Chan","year":"2013","unstructured":"Chan, S. S. et al. Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner. Cell Stem Cell 12, 587\u2013601, https:\/\/doi.org\/10.1016\/j.stem.2013.03.004 (2013).","journal-title":"Cell Stem Cell"},{"key":"45841_CR36","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1182\/blood.V95.5.1671.005k39_1671_1679","volume":"95","author":"CJ Drake","year":"2000","unstructured":"Drake, C. J. & Fleming, P. A. Vasculogenesis in the day 6.5 to 9.5 mouse embryo. Blood 95, 1671\u20131679 (2000).","journal-title":"Blood"},{"key":"45841_CR37","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.mod.2013.07.001","volume":"130","author":"M Kitagawa","year":"2013","unstructured":"Kitagawa, M. et al. Hes1 and Hes5 regulate vascular remodeling and arterial specification of endothelial cells in brain vascular development. Mech Dev 130, 458\u2013466, https:\/\/doi.org\/10.1016\/j.mod.2013.07.001 (2013).","journal-title":"Mech Dev"},{"key":"45841_CR38","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1182\/blood-2012-12-471649","volume":"122","author":"JB Lee","year":"2013","unstructured":"Lee, J. B. et al. Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embryonic and induced pluripotent stem cells. Blood 122, 1162\u20131173, https:\/\/doi.org\/10.1182\/blood-2012-12-471649 (2013).","journal-title":"Blood"},{"key":"45841_CR39","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1073\/pnas.1413234112","volume":"112","author":"R Morita","year":"2015","unstructured":"Morita, R. et al. ETS transcription factor ETV2 directly converts human fibroblasts into functional endothelial cells. Proc Natl Acad Sci USA 112, 160\u2013165, https:\/\/doi.org\/10.1073\/pnas.1413234112 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"45841_CR40","doi-asserted-by":"publisher","first-page":"13839","DOI":"10.1073\/pnas.1313192110","volume":"110","author":"M Xin","year":"2013","unstructured":"Xin, M. et al. Hippo pathway effector Yap promotes cardiac regeneration. Proc Natl Acad Sci USA 110, 13839\u201313844, https:\/\/doi.org\/10.1073\/pnas.1313192110 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"45841_CR41","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1016\/j.celrep.2016.04.027","volume":"15","author":"A Singh","year":"2016","unstructured":"Singh, A. et al. Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development. Cell Rep 15, 1384\u20131393, https:\/\/doi.org\/10.1016\/j.celrep.2016.04.027 (2016).","journal-title":"Cell Rep"},{"key":"45841_CR42","doi-asserted-by":"publisher","first-page":"ra70","DOI":"10.1126\/scisignal.2002278","volume":"4","author":"M Xin","year":"2011","unstructured":"Xin, M. et al. Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size. Sci Signal 4, ra70, https:\/\/doi.org\/10.1126\/scisignal.2002278 (2011).","journal-title":"Sci Signal"},{"key":"45841_CR43","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/S1097-2765(00)80221-X","volume":"4","author":"BP Eliceiri","year":"1999","unstructured":"Eliceiri, B. P. et al. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell 4, 915\u2013924 (1999).","journal-title":"Mol Cell"},{"key":"45841_CR44","doi-asserted-by":"publisher","first-page":"2895","DOI":"10.1242\/dev.02880","volume":"134","author":"T Kunath","year":"2007","unstructured":"Kunath, T. et al. FGF stimulation of the Erk1\/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment. Development 134, 2895\u20132902, https:\/\/doi.org\/10.1242\/dev.02880 (2007).","journal-title":"Development"},{"key":"45841_CR45","doi-asserted-by":"publisher","first-page":"18531","DOI":"10.1073\/pnas.0703113104","volume":"104","author":"A Klaus","year":"2007","unstructured":"Klaus, A., Saga, Y., Taketo, M. M., Tzahor, E. & Birchmeier, W. Distinct roles of Wnt\/beta-catenin and Bmp signaling during early cardiogenesis. Proc Natl Acad Sci USA 104, 18531\u201318536, https:\/\/doi.org\/10.1073\/pnas.0703113104 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"45841_CR46","doi-asserted-by":"publisher","first-page":"19812","DOI":"10.1073\/pnas.0605768103","volume":"103","author":"AT Naito","year":"2006","unstructured":"Naito, A. T. et al. Developmental stage-specific biphasic roles of Wnt\/beta-catenin signaling in cardiomyogenesis and hematopoiesis. Proc Natl Acad Sci USA 103, 19812\u201319817, https:\/\/doi.org\/10.1073\/pnas.0605768103 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"45841_CR47","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1242\/dev.050104","volume":"139","author":"Y Pei","year":"2012","unstructured":"Pei, Y. et al. WNT signaling increases proliferation and impairs differentiation of stem cells in the developing cerebellum. Development 139, 1724\u20131733, https:\/\/doi.org\/10.1242\/dev.050104 (2012).","journal-title":"Development"},{"key":"45841_CR48","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1089\/scd.2018.0049","volume":"27","author":"BN Singh","year":"2018","unstructured":"Singh, B. N., Weaver, C. V., Garry, M. G. & Garry, D. J. Hedgehog and Wnt Signaling Pathways Regulate Tail Regeneration. Stem Cells Dev 27, 1426\u20131437, https:\/\/doi.org\/10.1089\/scd.2018.0049 (2018).","journal-title":"Stem Cells Dev"},{"key":"45841_CR49","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.bbamcr.2009.11.009","volume":"1803","author":"BN Singh","year":"2010","unstructured":"Singh, B. N., Rao, K. S. & Rao Ch, M. Ubiquitin-proteasome-mediated degradation and synthesis of MyoD is modulated by alphaB-crystallin, a small heat shock protein, during muscle differentiation. Biochim Biophys Acta 1803, 288\u2013299, https:\/\/doi.org\/10.1016\/j.bbamcr.2009.11.009 (2010).","journal-title":"Biochim Biophys Acta"},{"key":"45841_CR50","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/j.jmb.2006.12.012","volume":"366","author":"BN Singh","year":"2007","unstructured":"Singh, B. N., Rao, K. S., Ramakrishna, T., Rangaraj, N. & Rao Ch, M. Association of alphaB-crystallin, a small heat shock protein, with actin: role in modulating actin filament dynamics in vivo. J Mol Biol 366, 756\u2013767, https:\/\/doi.org\/10.1016\/j.jmb.2006.12.012 (2007).","journal-title":"J Mol Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45841-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45841-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45841-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T11:17:18Z","timestamp":1671275838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45841-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,5]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["45841"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-45841-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,5]]},"assertion":[{"value":"11 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"9736"}}