{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:53:00Z","timestamp":1791219180145,"version":"4.1.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T00:00:00Z","timestamp":1460419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T00:00:00Z","timestamp":1460419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (\n                    <jats:italic>PTHrP<\/jats:italic>\n                    ) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I\/C (\n                    <jats:italic>Nfic<\/jats:italic>\n                    ). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP\u2013PPR system during root morphogenesis and tooth eruption.\n                  <\/jats:p>","DOI":"10.1038\/ncomms11277","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T05:13:23Z","timestamp":1460438003000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":150,"title":["Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation"],"prefix":"10.1038","volume":"7","author":[{"given":"Wanida","family":"Ono","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Sakagami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Nishimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry M.","family":"Kronenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,4,12]]},"reference":[{"key":"BFncomms11277_CR1","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1242\/jcs.00410","volume":"116","author":"I Thesleff","year":"2003","unstructured":"Thesleff, I. Epithelial\u2013mesenchymal signalling regulating tooth morphogenesis. J. Cell. Sci. 116, 1647\u20131648 (2003).","journal-title":"J. Cell. Sci."},{"key":"BFncomms11277_CR2","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1002\/dvdy.20674","volume":"235","author":"X Luan","year":"2006","unstructured":"Luan, X., Ito, Y. & Diekwisch, T. G. Evolution and development of Hertwig's epithelial root sheath. Dev. Dyn. 235, 1167\u20131180 (2006).","journal-title":"Dev. Dyn."},{"key":"BFncomms11277_CR3","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1177\/154405910808700509","volume":"87","author":"GE Wise","year":"2008","unstructured":"Wise, G. E. & King, G. J. Mechanisms of tooth eruption and orthodontic tooth movement. J. Dent. Res. 87, 414\u2013434 (2008).","journal-title":"J. Dent. Res."},{"key":"BFncomms11277_CR4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S0092-8674(01)00622-5","volume":"108","author":"K Nakashima","year":"2002","unstructured":"Nakashima, K. et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108, 17\u201329 (2002).","journal-title":"Cell"},{"key":"BFncomms11277_CR5","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/S0092-8674(00)80259-7","volume":"89","author":"F Otto","year":"1997","unstructured":"Otto, F. et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89, 765\u2013771 (1997).","journal-title":"Cell"},{"key":"BFncomms11277_CR6","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1177\/0022034509342873","volume":"88","author":"S Chen","year":"2009","unstructured":"Chen, S. et al. Runx2, osx, and dspp in tooth development. J. Dent. Res. 88, 904\u2013909 (2009).","journal-title":"J. Dent. Res."},{"key":"BFncomms11277_CR7","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1002\/jbmr.1552","volume":"27","author":"Z Cao","year":"2012","unstructured":"Cao, Z. et al. Genetic evidence for the vital function of Osterix in cementogenesis. J. Bone Miner. Res. 27, 1080\u20131092 (2012).","journal-title":"J. Bone Miner. Res."},{"key":"BFncomms11277_CR8","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.devcel.2010.07.010","volume":"19","author":"C Maes","year":"2010","unstructured":"Maes, C. et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev. Cell. 19, 329\u2013344 (2010).","journal-title":"Dev. Cell."},{"key":"BFncomms11277_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1196\/annals.1346.002","volume":"1068","author":"HM Kronenberg","year":"2006","unstructured":"Kronenberg, H. M. PTHrP and skeletal development. Ann. N. Y. Acad. Sci. 1068, 1\u201313 (2006).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"BFncomms11277_CR10","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1002\/jbmr.1617","volume":"27","author":"LK McCauley","year":"2012","unstructured":"McCauley, L. K. & Martin, T. J. Twenty-five years of PTHrP progress: from cancer hormone to multifunctional cytokine. J. Bone Miner. Res. 27, 1231\u20131239 (2012).","journal-title":"J. Bone Miner. Res."},{"key":"BFncomms11277_CR11","doi-asserted-by":"publisher","first-page":"5751","DOI":"10.1128\/MCB.00415-09","volume":"29","author":"E Kozhemyakina","year":"2009","unstructured":"Kozhemyakina, E., Cohen, T., Yao, T. P. & Lassar, A. B. Parathyroid hormone-related peptide represses chondrocyte hypertrophy through a protein phosphatase 2A\/histone deacetylase 4\/MEF2 pathway. Mol. Cell. Biol. 29, 5751\u20135762 (2009).","journal-title":"Mol. Cell. Biol."},{"key":"BFncomms11277_CR12","doi-asserted-by":"publisher","first-page":"3492","DOI":"10.1172\/JCI46406","volume":"121","author":"JY Wu","year":"2011","unstructured":"Wu, J. Y. et al. Gsalpha enhances commitment of mesenchymal progenitors to the osteoblast lineage but restrains osteoblast differentiation in mice. J. Clin. Invest. 121, 3492\u20133504 (2011).","journal-title":"J. Clin. Invest."},{"key":"BFncomms11277_CR13","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.ajhg.2008.11.006","volume":"83","author":"E Decker","year":"2008","unstructured":"Decker, E. et al. PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. Am. J. Hum. Genet. 83, 781\u2013786 (2008).","journal-title":"Am. J. Hum. Genet."},{"key":"BFncomms11277_CR14","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1002\/jbmr.385","volume":"26","author":"T Yamaguchi","year":"2011","unstructured":"Yamaguchi, T. et al. Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese. J. Bone Miner. Res. 26, 1655\u20131661 (2011).","journal-title":"J. Bone Miner. Res."},{"key":"BFncomms11277_CR15","doi-asserted-by":"publisher","first-page":"11846","DOI":"10.1073\/pnas.95.20.11846","volume":"95","author":"WM Philbrick","year":"1998","unstructured":"Philbrick, W. M., Dreyer, B. E., Nakchbandi, I. A. & Karaplis, A. C. Parathyroid hormone-related protein is required for tooth eruption. Proc. Natl. Acad. Sci. USA. 95, 11846\u201311851 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"BFncomms11277_CR16","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1359\/jbmr.2000.15.11.2140","volume":"15","author":"H Ouyang","year":"2000","unstructured":"Ouyang, H. et al. Parathyroid hormone-related protein regulates extracellular matrix gene expression in cementoblasts and inhibits cementoblast-mediated mineralization in vitro. J. Bone Miner. Res. 15, 2140\u20132153 (2000).","journal-title":"J. Bone Miner. Res."},{"key":"BFncomms11277_CR17","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1111\/j.1469-7580.2011.01367.x","volume":"218","author":"V Lungova","year":"2011","unstructured":"Lungova, V. et al. Tooth-bone morphogenesis during postnatal stages of mouse first molar development. J. Anat. 218, 699\u2013716 (2011).","journal-title":"J. Anat."},{"key":"BFncomms11277_CR18","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1359\/JBMR.051005","volume":"21","author":"X Chen","year":"2006","unstructured":"Chen, X. et al. Initial characterization of PTH-related protein gene-driven lacZ expression in the mouse. J. Bone Miner. Res. 21, 113\u2013123 (2006).","journal-title":"J. Bone Miner. Res."},{"key":"BFncomms11277_CR19","doi-asserted-by":"publisher","first-page":"3231","DOI":"10.1242\/dev.02480","volume":"133","author":"SJ Rodda","year":"2006","unstructured":"Rodda, S. J. & McMahon, A. P. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133, 3231\u20133244 (2006).","journal-title":"Development"},{"key":"BFncomms11277_CR20","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1242\/dev.129.12.2977","volume":"129","author":"T Kobayashi","year":"2002","unstructured":"Kobayashi, T. et al. PTHrP and Indian hedgehog control differentiation of growth plate chondrocytes at multiple steps. Development 129, 2977\u20132986 (2002).","journal-title":"Development"},{"key":"BFncomms11277_CR21","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1002\/dvdy.10453","volume":"229","author":"A Kruzynska-Frejtag","year":"2004","unstructured":"Kruzynska-Frejtag, A. et al. Periostin is expressed within the developing teeth at the sites of epithelial\u2013mesenchymal interaction. Dev. Dyn. 229, 857\u2013868 (2004).","journal-title":"Dev. Dyn."},{"key":"BFncomms11277_CR22","doi-asserted-by":"publisher","first-page":"44005","DOI":"10.1074\/jbc.M208265200","volume":"277","author":"M Zhang","year":"2002","unstructured":"Zhang, M. et al. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J. Biol. Chem. 277, 44005\u201344012 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFncomms11277_CR23","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1177\/154405910708600404","volume":"86","author":"Y Lu","year":"2007","unstructured":"Lu, Y. et al. DMP1-targeted Cre expression in odontoblasts and osteocytes. J. Dent. Res. 86, 320\u2013325 (2007).","journal-title":"J. Dent. Res."},{"key":"BFncomms11277_CR24","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1172\/JCI11296","volume":"107","author":"LM Calvi","year":"2001","unstructured":"Calvi, L. M. et al. Activated parathyroid hormone\/parathyroid hormone-related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone. J. Clin. Invest. 107, 277\u2013286 (2001).","journal-title":"J. Clin. Invest."},{"key":"BFncomms11277_CR25","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.mod.2004.02.004","volume":"121","author":"LM Calvi","year":"2004","unstructured":"Calvi, L. M. et al. Constitutively active PTH\/PTHrP receptor in odontoblasts alters odontoblast and ameloblast function and maturation. Mech. Dev. 121, 397\u2013408 (2004).","journal-title":"Mech. Dev."},{"key":"BFncomms11277_CR26","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.bbrc.2007.04.031","volume":"357","author":"W Techawattanawisal","year":"2007","unstructured":"Techawattanawisal, W. et al. Isolation of multipotent stem cells from adult rat periodontal ligament by neurosphere-forming culture system. Biochem. Biophys. Res. Commun. 357, 917\u2013923 (2007).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFncomms11277_CR27","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1128\/MCB.23.3.1075-1084.2003","volume":"23","author":"G Steele-Perkins","year":"2003","unstructured":"Steele-Perkins, G. et al. Essential role for NFI-C\/CTF transcription-replication factor in tooth root development. Mol. Cell. Biol. 23, 1075\u20131084 (2003).","journal-title":"Mol. Cell. Biol."},{"key":"BFncomms11277_CR28","doi-asserted-by":"publisher","first-page":"9616","DOI":"10.1074\/jbc.M109.094862","volume":"285","author":"E Shimizu","year":"2010","unstructured":"Shimizu, E., Selvamurugan, N., Westendorf, J. J., Olson, E. N. & Partridge, N. C. HDAC4 represses matrix metalloproteinase-13 transcription in osteoblastic cells, and parathyroid hormone controls this repression. J. Biol. Chem. 285, 9616\u20139626 (2010).","journal-title":"J. Biol. Chem."},{"key":"BFncomms11277_CR29","doi-asserted-by":"publisher","first-page":"21340","DOI":"10.1074\/jbc.M114.550699","volume":"289","author":"E Shimizu","year":"2014","unstructured":"Shimizu, E., Nakatani, T., He, Z. & Partridge, N. C. Parathyroid hormone regulates HDAC4 through PKA-mediated phosphorylation and dephosphorylation in osteoblastic cells. J. Biol. Chem. 289, 21340\u201321350 (2014).","journal-title":"J. Biol. Chem."},{"key":"BFncomms11277_CR30","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.cell.2004.10.024","volume":"119","author":"RB Vega","year":"2004","unstructured":"Vega, R. B. et al. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell 119, 555\u2013566 (2004).","journal-title":"Cell"},{"key":"BFncomms11277_CR31","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1172\/JCI31960","volume":"117","author":"MJ Potthoff","year":"2007","unstructured":"Potthoff, M. J. et al. Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J. Clin. Invest. 117, 2459\u20132467 (2007).","journal-title":"J. Clin. Invest."},{"key":"BFncomms11277_CR32","first-page":"695","volume":"45","author":"TG Diekwisch","year":"2001","unstructured":"Diekwisch, T. G. The developmental biology of cementum. Int. J. Dev. Biol. 45, 695\u2013706 (2001).","journal-title":"Int. J. Dev. Biol."},{"key":"BFncomms11277_CR33","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.aanat.2009.07.004","volume":"191","author":"T Yamamoto","year":"2009","unstructured":"Yamamoto, T. & Takahashi, S. Hertwig's epithelial root sheath cells do not transform into cementoblasts in rat molar cementogenesis. Ann. Anat 191, 547\u2013555 (2009).","journal-title":"Ann. Anat"},{"key":"BFncomms11277_CR34","doi-asserted-by":"publisher","first-page":"17293","DOI":"10.1074\/jbc.M109.009084","volume":"284","author":"DS Lee","year":"2009","unstructured":"Lee, D. S. et al. Nuclear factor I-C is essential for odontogenic cell proliferation and odontoblast differentiation during tooth root development. J. Biol. Chem. 284, 17293\u201317303 (2009).","journal-title":"J. Biol. Chem."},{"key":"BFncomms11277_CR35","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1177\/154405910608500506","volume":"85","author":"M Nakatomi","year":"2006","unstructured":"Nakatomi, M., Morita, I., Eto, K. & Ota, M. S. Sonic hedgehog signaling is important in tooth root development. J. Dent. Res. 85, 427\u2013431 (2006).","journal-title":"J. Dent. Res."},{"key":"BFncomms11277_CR36","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1359\/jbmr.091103","volume":"25","author":"X Huang","year":"2010","unstructured":"Huang, X., Xu, X., Bringas, P. Jr, Hung, Y. P. & Chai, Y. Smad4-Shh-Nfic signaling cascade-mediated epithelial\u2013mesenchymal interaction is crucial in regulating tooth root development. J. Bone Miner. Res. 25, 1167\u20131178 (2010).","journal-title":"J. Bone Miner. Res."},{"key":"BFncomms11277_CR37","doi-asserted-by":"publisher","first-page":"3374","DOI":"10.1242\/dev.127068","volume":"142","author":"Y Liu","year":"2015","unstructured":"Liu, Y. et al. An Nfic-hedgehog signaling cascade regulates tooth root development. Development 142, 3374\u20133382 (2015).","journal-title":"Development"},{"key":"BFncomms11277_CR38","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1177\/0022034512470137","volume":"92","author":"TH Kim","year":"2013","unstructured":"Kim, T. H. et al. Beta-catenin is required in odontoblasts for tooth root formation. J. Dent. Res. 92, 215\u2013221 (2013).","journal-title":"J. Dent. Res."},{"key":"BFncomms11277_CR39","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/ijos.2013.41","volume":"5","author":"A Rakian","year":"2013","unstructured":"Rakian, A. et al. Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium. Int. J. Oral Sci 5, 75\u201384 (2013).","journal-title":"Int. J. Oral Sci"},{"key":"BFncomms11277_CR40","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ydbio.2013.08.003","volume":"382","author":"Y Wang","year":"2013","unstructured":"Wang, Y., Cox, M. K., Coricor, G., MacDougall, M. & Serra, R. Inactivation of Tgfbr2 in Osterix-Cre expressing dental mesenchyme disrupts molar root formation. Dev. Biol. 382, 27\u201337 (2013).","journal-title":"Dev. Biol."},{"key":"BFncomms11277_CR41","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1600-0714.1987.tb02060.x","volume":"16","author":"SC Marks Jr","year":"1987","unstructured":"Marks, S. C. Jr & Cahill, D. R. Regional control by the dental follicle of alterations in alveolar bone metabolism during tooth eruption. J. Oral Pathol 16, 164\u2013169 (1987).","journal-title":"J. Oral Pathol"},{"key":"BFncomms11277_CR42","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.ajodo.2009.10.021","volume":"137","author":"SA Frazier-Bowers","year":"2010","unstructured":"Frazier-Bowers, S. A., Simmons, D., Wright, J. T., Proffit, W. R. & Ackerman, J. L. Primary failure of eruption and PTH1R: the importance of a genetic diagnosis for orthodontic treatment planning. Am. J. Orthod. Dentofacial Orthop. 137, 160 e1-7; discussion 160-1 (2010).","journal-title":"Am. J. Orthod. Dentofacial Orthop."},{"key":"BFncomms11277_CR43","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1126\/science.273.5275.663","volume":"273","author":"B Lanske","year":"1996","unstructured":"Lanske, B. et al. PTH\/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Science 273, 663\u2013666 (1996).","journal-title":"Science"},{"key":"BFncomms11277_CR44","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/S8756-3282(02)00912-2","volume":"31","author":"Z Kalajzic","year":"2002","unstructured":"Kalajzic, Z. et al. Directing the expression of a green fluorescent protein transgene in differentiated osteoblasts: comparison between rat type I collagen and rat osteocalcin promoters. Bone 31, 654\u2013660 (2002).","journal-title":"Bone"},{"key":"BFncomms11277_CR45","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1359\/jbmr.2002.17.1.15","volume":"17","author":"I Kalajzic","year":"2002","unstructured":"Kalajzic, I. et al. Use of type I collagen green fluorescent protein transgenes to identify subpopulations of cells at different stages of the osteoblast lineage. J. Bone Miner. Res. 17, 15\u201325 (2002).","journal-title":"J. Bone Miner. Res."},{"key":"BFncomms11277_CR46","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nn.2467","volume":"13","author":"L Madisen","year":"2010","unstructured":"Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133\u2013140 (2010).","journal-title":"Nat. Neurosci."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms11277.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms11277","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms11277.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T13:25:26Z","timestamp":1718457926000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms11277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,12]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,1]]}},"alternative-id":["BFncomms11277"],"URL":"https:\/\/doi.org\/10.1038\/ncomms11277","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,12]]},"assertion":[{"value":"25 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11277"}}