{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:41:58Z","timestamp":1790649718211,"version":"4.1.0"},"reference-count":81,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1454 \u2010 project number 432325352"],"award-info":[{"award-number":["SFB 1454 \u2010 project number 432325352"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR83 \u2010 project number 112927078"],"award-info":[{"award-number":["TRR83 \u2010 project number 112927078"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SPP1926"],"award-info":[{"award-number":["SPP1926"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SPP1726"],"award-info":[{"award-number":["SPP1726"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2743"],"award-info":[{"award-number":["FOR2743"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB894\/TP\u2010A22"],"award-info":[{"award-number":["SFB894\/TP\u2010A22"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["under Germany's Excellence Strategy \u2010 EXC2151 \u2010 project number 390873048"],"award-info":[{"award-number":["under Germany's Excellence Strategy \u2010 EXC2151 \u2010 project number 390873048"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001645","name":"Boehringer Ingelheim Fonds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Rep"],"published-print":{"date-parts":[[2022,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The primary cilium constitutes an organelle that orchestrates signal transduction independently from the cell body. Dysregulation of this intricate molecular architecture leads to severe human diseases, commonly referred to as ciliopathies. However, the molecular underpinnings how ciliary signaling orchestrates a specific cellular output remain elusive. By combining spatially resolved optogenetics with RNA sequencing and imaging, we reveal a novel cAMP signalosome that is functionally distinct from the cytoplasm. We identify the genes and pathways targeted by the ciliary cAMP signalosome and shed light on the underlying mechanisms and downstream signaling. We reveal that chronic stimulation of the ciliary cAMP signalosome transforms kidney epithelia from tubules into cysts. Counteracting this chronic cAMP elevation in the cilium by small molecules targeting activation of phosphodiesterase\u20104 long isoforms inhibits cyst growth. Thereby, we identify a novel concept of how the primary cilium controls cellular functions and maintains tissue integrity in a specific and spatially distinct manner and reveal novel molecular components that might be involved in the development of one of the most common genetic diseases, polycystic kidney disease.<\/jats:p>","DOI":"10.15252\/embr.202154315","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T05:29:55Z","timestamp":1655098195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation"],"prefix":"10.1038","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0489-7535","authenticated-orcid":false,"given":"Jan N","family":"Hansen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Leyendecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birthe","family":"St\u00fcven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens\u2010Henning","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Derakhshandeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaazba","family":"Irfan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9016-5989","authenticated-orcid":false,"given":"Tommy J","family":"Sroka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenley M","family":"Preval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paurav B","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kraut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Theis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Dorothee","family":"Drews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0336-8284","authenticated-orcid":false,"given":"Elena","family":"De\u2010Domenico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"H\u00e4ndler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6285-8796","authenticated-orcid":false,"given":"Gregory J","family":"Pazour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J P","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1427-9412","authenticated-orcid":false,"given":"David U","family":"Mick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4800-6332","authenticated-orcid":false,"given":"Dagmar","family":"Wachten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"BFEMBR202154315_CR1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41581-019-0116-9","volume":"15","author":"Z Anvarian","year":"2019","unstructured":"Anvarian Z, Mykytyn K, Mukhopadhyay S, Pedersen LB, Christensen ST (2019) Cellular signalling by primary cilia in development, organ function and disease. Nat Rev Nephrol 15: 199\u2013219","journal-title":"Nat Rev Nephrol"},{"key":"BFEMBR202154315_CR2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3001191","volume":"19","author":"CD Arveseth","year":"2021","unstructured":"Arveseth CD, Happ JT, Hedeen DS, Zhu J\u2010F, Capener JL, Klatt Shaw D, Deshpande I, Liang J, Xu J, Stubben SL et\u2009al (2021) Smoothened transduces Hedgehog signals via activity\u2010dependent sequestration of PKA catalytic subunits. PLoS Biol 19: e3001191","journal-title":"PLoS Biol"},{"key":"BFEMBR202154315_CR3","doi-asserted-by":"crossref","first-page":"7786","DOI":"10.1073\/pnas.1608061113","volume":"113","author":"VA Bachmann","year":"2016","unstructured":"Bachmann VA, Mayrhofer JE, Ilouz R, Tschaikner P, Raffeiner P, R\u00f6ck R, Courcelles M, Apelt F, Lu T\u2010W, Baillie GS et\u2009al (2016) Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling. Proc Natl Acad Sci USA 113: 7786\u20137791","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202154315_CR4","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1111\/j.1742-4658.2009.06926.x","volume":"276","author":"GS Baillie","year":"2009","unstructured":"Baillie GS (2009) Compartmentalized signalling: spatial regulation of cAMP by the action of compartmentalized phosphodiesterases. FEBS J 276: 1790\u20131799","journal-title":"FEBS J"},{"key":"BFEMBR202154315_CR5","doi-asserted-by":"crossref","first-page":"a028175","DOI":"10.1101\/cshperspect.a028175","volume":"9","author":"F Bangs","year":"2017","unstructured":"Bangs F, Anderson KV (2017) Primary cilia and mammalian hedgehog signaling. Cold Spring Harb Perspect Biol 9: a028175","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"BFEMBR202154315_CR6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fped.2017.00221","volume":"5","author":"C Bergmann","year":"2017","unstructured":"Bergmann C (2017) Genetics of autosomal recessive polycystic kidney disease and its differential diagnoses. Front Pediatr 5: 221","journal-title":"Front Pediatr"},{"key":"BFEMBR202154315_CR7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0137652","volume":"10","author":"HM Beyer","year":"2015","unstructured":"Beyer HM, Gonschorek P, Samodelov SL, Meier M, Weber W, Zurbriggen MD (2015) AQUA cloning: a versatile and simple enzyme\u2010free cloning approach. PLoS One 10: e0137652","journal-title":"PLoS One"},{"key":"BFEMBR202154315_CR8","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/cne.21510","volume":"505","author":"GA Bishop","year":"2007","unstructured":"Bishop GA, Berbari NF, Lewis J, Mykytyn K (2007) Type III adenylyl cyclase localizes to primary cilia throughout the adult mouse brain. J Comp Neurol 505: 562\u2013571","journal-title":"J Comp Neurol"},{"key":"BFEMBR202154315_CR9","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s40265-019-1056-1","volume":"79","author":"HA Blair","year":"2019","unstructured":"Blair HA (2019) Tolvaptan: a review in autosomal dominant polycystic kidney disease. Drugs 79: 303\u2013313","journal-title":"Drugs"},{"key":"BFEMBR202154315_CR10","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.acvd.2016.02.004","volume":"109","author":"P Bobin","year":"2016","unstructured":"Bobin P, Belacel\u2010Ouari M, Bedioune I, Zhang L, Leroy J, Leblais V, Fischmeister R, Vandecasteele G (2016) Cyclic nucleotide phosphodiesterases in heart and vessels: a therapeutic perspective. Arch Cardiovasc Dis 109: 431\u2013443","journal-title":"Arch Cardiovasc Dis"},{"key":"BFEMBR202154315_CR11","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/ncb2117","volume":"12","author":"C Boehlke","year":"2010","unstructured":"Boehlke C, Kotsis F, Patel V, Braeg S, Voelker H, Bredt S, Beyer T, Janusch H, Hamann C, G\u00f6del M et\u2009al (2010) Primary cilia regulate mTORC1 activity and cell size through Lkb1. Nat Cell Biol 12: 1115\u20131122","journal-title":"Nat Cell Biol"},{"key":"BFEMBR202154315_CR12","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","volume":"34","author":"NL Bray","year":"2016","unstructured":"Bray NL, Pimentel H, Melsted P, Pachter L (2016) Near\u2010optimal probabilistic RNA\u2010seq quantification. Nat Biotechnol 34: 525\u2013527","journal-title":"Nat Biotechnol"},{"key":"BFEMBR202154315_CR13","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1146\/annurev.physiol.63.1.579","volume":"63","author":"MD Breyer","year":"2001","unstructured":"Breyer MD, Breyer RM (2001) G protein\u2010coupled prostanoid receptors and the kidney. Annu Rev Physiol 63: 579\u2013605","journal-title":"Annu Rev Physiol"},{"key":"BFEMBR202154315_CR14","volume-title":"Polycystic kidney disease","author":"JP Calvet","year":"2015","unstructured":"Calvet JP (2015) The role of calcium and cyclic AMP in PKD. In Polycystic kidney disease, Li X (ed), Brisbane: Codon Publications"},{"key":"BFEMBR202154315_CR15","first-page":"601","volume":"32","author":"SV Carrillo","year":"1982","unstructured":"Carrillo SV, Rossi MA, Muccillo G (1982) Morphological and biochemical changes of the heart in experimental hypochromic anemia in rats. Arch Latinoam Nutr 32: 601\u2013616","journal-title":"Arch Latinoam Nutr"},{"key":"BFEMBR202154315_CR16","doi-asserted-by":"crossref","first-page":"10679","DOI":"10.1073\/pnas.1016214108","volume":"108","author":"YH Choi","year":"2011","unstructured":"Choi YH, Suzuki A, Hajarnis S, Ma Z, Chapin HC, Caplan MJ, Pontoglio M, Somlo S, Igarashi P (2011) Polycystin\u20102 and phosphodiesterase 4C are components of a ciliary A\u2010kinase anchoring protein complex that is disrupted in cystic kidney diseases. Proc Natl Acad Sci USA 108: 10679\u201310684","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202154315_CR17","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1074\/jbc.R200029200","volume":"278","author":"M Conti","year":"2003","unstructured":"Conti M, Richter W, Mehats C, Livera G, Park JY, Jin C (2003) Cyclic AMP\u2010specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling. J Biol Chem 278: 5493\u20135496","journal-title":"J Biol Chem"},{"key":"BFEMBR202154315_CR18","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nbt.3437","volume":"34","author":"JG Doench","year":"2016","unstructured":"Doench JG, Fusi N, Sullender M, Hegde M, Vaimberg EW, Donovan KF, Smith I, Tothova Z, Wilen C, Orchard R et\u2009al (2016) Optimized sgRNA design to maximize activity and minimize off\u2010target effects of CRISPR\u2010Cas9. Nat Biotechnol 34: 184\u2013191","journal-title":"Nat Biotechnol"},{"key":"BFEMBR202154315_CR19","doi-asserted-by":"crossref","first-page":"8463","DOI":"10.1128\/JVI.72.11.8463-8471.1998","volume":"72","author":"T Dull","year":"1998","unstructured":"Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D, Naldini L (1998) A third\u2010generation lentivirus vector with a conditional packaging system. J\u2009Virol 72: 8463\u20138471","journal-title":"J\u2009Virol"},{"key":"BFEMBR202154315_CR20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.devcel.2014.09.011","volume":"31","author":"T Eguether","year":"2014","unstructured":"Eguether T, San Agustin J, Keady B, Jonassen J, Liang Y, Francis R, Tobita K, Johnson C, Abdelhamed Z, Lo C et\u2009al (2014) IFT27 links the BBSome to IFT for maintenance of the ciliary signaling compartment. Dev Cell 31: 279\u2013290","journal-title":"Dev Cell"},{"key":"BFEMBR202154315_CR21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.prostaglandins.2012.03.005","volume":"98","author":"D Elberg","year":"2012","unstructured":"Elberg D, Turman MA, Pullen N, Elberg G (2012) Prostaglandin E2 stimulates cystogenesis through EP4 receptor in IMCD\u20103 cells. Prostaglandins Other Lipid Mediat 98: 11\u201316","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"BFEMBR202154315_CR22","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s12859-017-1559-2","volume":"18","author":"A Fabregat","year":"2017","unstructured":"Fabregat A, Sidiropoulos K, Viteri G, Forner O, Marin\u2010Garcia P, Arnau V, D'Eustachio P, Stein L, Hermjakob H (2017) Reactome pathway analysis: a high\u2010performance in\u2010memory approach. BMC Bioinformatics 18: 142","journal-title":"BMC Bioinformatics"},{"key":"BFEMBR202154315_CR23","doi-asserted-by":"crossref","DOI":"10.1002\/wdev.377","volume":"9","author":"ED Gigante","year":"2020","unstructured":"Gigante ED, Caspary T (2020) Signaling in the primary cilium through the lens of the Hedgehog pathway. Wiley Interdiscip Rev Dev Biol 9: e377","journal-title":"Wiley Interdiscip Rev Dev Biol"},{"key":"BFEMBR202154315_CR24","doi-asserted-by":"crossref","first-page":"F1034","DOI":"10.1152\/ajprenal.00195.2003","volume":"285","author":"LM Guay\u2010Woodford","year":"2003","unstructured":"Guay\u2010Woodford LM (2003) Murine models of polycystic kidney disease: molecular and therapeutic insights. Am J Physiol Renal Physiol 285: F1034\u2013F1049","journal-title":"Am J Physiol Renal Physiol"},{"key":"BFEMBR202154315_CR25","volume":"9","author":"JN Hansen","year":"2020","unstructured":"Hansen JN, Kaiser F, Klausen C, St\u00fcven B, Chong R, B\u00f6nigk W, Mick DU, M\u00f6glich A, Jurisch\u2010Yaksi N, Schmidt FI et\u2009al (2020) Nanobody\u2010directed targeting of optogenetic tools to study signaling in the primary cilium. eLife 9: e57907","journal-title":"eLife"},{"key":"BFEMBR202154315_CR26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1140\/epje\/s10189-021-00031-y","volume":"44","author":"JN Hansen","year":"2021","unstructured":"Hansen JN, Rassmann S, Stuven B, Jurisch\u2010Yaksi N, Wachten D (2021) CiliaQ: a simple, open\u2010source software for automated quantification of ciliary morphology and fluorescence in 2D, 3D, and 4D images. Eur Phys J E Soft Matter 44: 18","journal-title":"Eur Phys J E Soft Matter"},{"key":"BFEMBR202154315_CR27","doi-asserted-by":"crossref","DOI":"10.1371\/annotation\/e608601c-eadd-4c11-adb2-7b605aba9c44","volume":"7","author":"M Hansen","year":"2012","unstructured":"Hansen M, Gerds TA, Nielsen OH, Seidelin JB, Troelsen JT, Olsen J (2012) pcaGoPromoter\u2013an R package for biological and regulatory interpretation of principal components in genome\u2010wide gene expression data. PLoS One 7: e32394","journal-title":"PLoS One"},{"key":"BFEMBR202154315_CR28","doi-asserted-by":"crossref","first-page":"7351","DOI":"10.1038\/s41598-017-07820-6","volume":"7","author":"K Harada","year":"2017","unstructured":"Harada K, Ito M, Wang X, Tanaka M, Wongso D, Konno A, Hirai H, Hirase H, Tsuboi T, Kitaguchi T (2017) Red fluorescent protein\u2010based cAMP indicator applicable to optogenetics and in\u2009vivo imaging. Sci Rep 7: 7351","journal-title":"Sci Rep"},{"key":"BFEMBR202154315_CR29","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1038\/bjc.2014.22","volume":"110","author":"DJ Henderson","year":"2014","unstructured":"Henderson DJ, Byrne A, Dulla K, Jenster G, Hoffmann R, Baillie GS, Houslay MD (2014) The cAMP phosphodiesterase\u20104D7 (PDE4D7) is downregulated in androgen\u2010independent prostate cancer cells and mediates proliferation by compartmentalising cAMP at the plasma membrane of VCaP prostate cancer cells. Br J Cancer 110: 1278\u20131287","journal-title":"Br J Cancer"},{"key":"BFEMBR202154315_CR30","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1056\/NEJMra1010172","volume":"364","author":"F Hildebrandt","year":"2011","unstructured":"Hildebrandt F, Benzing T, Katsanis N (2011) Ciliopathies. N Engl J Med 364: 1533\u20131543","journal-title":"N Engl J Med"},{"key":"BFEMBR202154315_CR31","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ceb.2016.02.008","volume":"39","author":"KI Hilgendorf","year":"2016","unstructured":"Hilgendorf KI, Johnson CT, Jackson PK (2016) The primary cilium as a cellular receiver: organizing ciliary GPCR signaling. Curr Opin Cell Biol 39: 84\u201392","journal-title":"Curr Opin Cell Biol"},{"key":"BFEMBR202154315_CR32","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.tibs.2009.09.007","volume":"35","author":"MD Houslay","year":"2010","unstructured":"Houslay MD (2010) Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends Biochem Sci 35: 91\u2013100","journal-title":"Trends Biochem Sci"},{"key":"BFEMBR202154315_CR33","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1161\/01.RES.0000261934.56938.38","volume":"100","author":"MD Houslay","year":"2007","unstructured":"Houslay MD, Baillie GS, Maurice DH (2007) cAMP\u2010Specific phosphodiesterase\u20104 enzymes in the cardiovascular system: a molecular toolbox for generating compartmentalized cAMP signaling. Circ Res 100: 950\u2013966","journal-title":"Circ Res"},{"key":"BFEMBR202154315_CR34","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nature02061","volume":"426","author":"D Huangfu","year":"2003","unstructured":"Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV (2003) Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426: 83\u201387","journal-title":"Nature"},{"key":"BFEMBR202154315_CR35","first-page":"D498","volume":"48","author":"B Jassal","year":"2020","unstructured":"Jassal B, Matthews L, Viteri G, Gong C, Lorente P, Fabregat A, Sidiropoulos K, Cook J, Gillespie M, Haw R et\u2009al (2020) The reactome pathway knowledgebase. Nucleic Acids Res 48: D498\u2013D503","journal-title":"Nucleic Acids Res"},{"key":"BFEMBR202154315_CR36","doi-asserted-by":"crossref","first-page":"12066","DOI":"10.1073\/pnas.1819730116","volume":"116","author":"JY Jiang","year":"2019","unstructured":"Jiang JY, Falcone JL, Curci S, Hofer AM (2019) Direct visualization of cAMP signaling in primary cilia reveals up\u2010regulation of ciliary GPCR activity following Hedgehog activation. Proc Natl Acad Sci USA 116: 12066\u201312071","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202154315_CR37","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/ncb3029","volume":"16","author":"D Jin","year":"2014","unstructured":"Jin D, Ni TT, Sun J, Wan H, Amack JD, Yu G, Fleming J, Chiang C, Li W, Papierniak A et\u2009al (2014) Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport. Nat Cell Biol 16: 841\u2013851","journal-title":"Nat Cell Biol"},{"key":"BFEMBR202154315_CR38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.devcel.2014.09.004","volume":"31","author":"GM Liew","year":"2014","unstructured":"Liew GM, Ye F, Nager AR, Murphy JP, Lee JS, Aguiar M, Breslow DK, Gygi SP, Nachury MV (2014) The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6\/BBS3. Dev Cell 31: 265\u2013278","journal-title":"Dev Cell"},{"key":"BFEMBR202154315_CR39","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA\u2010seq data with DESeq2. Genome Biol 15: 550","journal-title":"Genome Biol"},{"key":"BFEMBR202154315_CR40","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1124\/jpet.102.042218","volume":"304","author":"R Macianskiene","year":"2003","unstructured":"Macianskiene R, Viappiani S, Sipido KR, Mubagwa K (2003) Slowing of the inactivation of cardiac voltage\u2010dependent sodium channels by the amiodarone derivative 2\u2010methyl\u20103\u2010(3,5\u2010diiodo\u20104\u2010carboxymethoxybenzyl)benzofuran (KB130015). J Pharmacol Exp Ther 304: 130\u2013138","journal-title":"J Pharmacol Exp Ther"},{"key":"BFEMBR202154315_CR41","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202007207","author":"EA May","year":"2021","unstructured":"May EA, Kalocsay M, D\u2019Auriac IG, Schuster PS, Gygi SP, Nachury MV, Mick DU (2021) Time\u2010resolved proteomics profiling of the ciliary Hedgehog response. J Cell Biol 220 https:\/\/doi.org\/10.1083\/jcb.202007207","journal-title":"J Cell Biol"},{"key":"BFEMBR202154315_CR42","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1053\/j.ajkd.2020.08.012","volume":"77","author":"DJ McConnachie","year":"2021","unstructured":"McConnachie DJ, Stow JL, Mallett AJ (2021) Ciliopathies and the kidney: a review. Am J Kidney Dis 77: 410\u2013419","journal-title":"Am J Kidney Dis"},{"key":"BFEMBR202154315_CR43","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1016\/j.ddmec.2013.10.002","volume":"10","author":"LF Menezes","year":"2013","unstructured":"Menezes LF, Germino GG (2013) Murine models of polycystic kidney disease. Drug Discov Today Dis Mech 10: e153\u2013e158","journal-title":"Drug Discov Today Dis Mech"},{"key":"BFEMBR202154315_CR44","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.devcel.2015.10.015","volume":"35","author":"DU Mick","year":"2015","unstructured":"Mick DU, Rodrigues RB, Leib RD, Adams CM, Chien AS, Gygi SP, Nachury MV (2015) Proteomics of primary cilia by proximity labeling. Dev Cell 35: 497\u2013512","journal-title":"Dev Cell"},{"key":"BFEMBR202154315_CR45","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1146\/annurev.biochem.66.1.807","volume":"66","author":"M Montminy","year":"1997","unstructured":"Montminy M (1997) Transcriptional regulation by cyclic AMP. Annu Rev Biochem 66: 807\u2013822","journal-title":"Annu Rev Biochem"},{"key":"BFEMBR202154315_CR46","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.cell.2012.12.026","volume":"152","author":"S Mukhopadhyay","year":"2013","unstructured":"Mukhopadhyay S, Wen X, Ratti N, Loktev A, Rangell L, Scales SJ, Jackson PK (2013) The ciliary G\u2010protein\u2010coupled receptor Gpr161 negatively regulates the Sonic hedgehog pathway via cAMP signaling. Cell 152: 210\u2013223","journal-title":"Cell"},{"key":"BFEMBR202154315_CR47","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.tips.2017.11.006","volume":"39","author":"N Musheshe","year":"2018","unstructured":"Musheshe N, Schmidt M, Zaccolo M (2018) cAMP: from long\u2010range second messenger to nanodomain signalling. Trends Pharmacol Sci 39: 209\u2013222","journal-title":"Trends Pharmacol Sci"},{"key":"BFEMBR202154315_CR48","doi-asserted-by":"crossref","first-page":"a028183","DOI":"10.1101\/cshperspect.a028183","volume":"9","author":"K Mykytyn","year":"2017","unstructured":"Mykytyn K, Askwith C (2017) G\u2010protein\u2010coupled receptor signaling in cilia. Cold Spring Harb Perspect Biol 9: a028183","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"BFEMBR202154315_CR49","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ceb.2018.03.004","volume":"51","author":"MV Nachury","year":"2018","unstructured":"Nachury MV (2018) The molecular machines that traffic signaling receptors into and out of cilia. Curr Opin Cell Biol 51: 124\u2013131","journal-title":"Curr Opin Cell Biol"},{"key":"BFEMBR202154315_CR50","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41580-019-0116-4","volume":"20","author":"MV Nachury","year":"2019","unstructured":"Nachury MV, Mick DU (2019) Establishing and regulating the composition of cilia for signal transduction. Nat Rev Mol Cell Biol 20: 389\u2013405","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFEMBR202154315_CR51","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1538\/expanim.61.477","volume":"61","author":"S Nagao","year":"2012","unstructured":"Nagao S, Kugita M, Yoshihara D, Yamaguchi T (2012) Animal models for human polycystic kidney disease. Exp Anim 61: 477\u2013488","journal-title":"Exp Anim"},{"key":"BFEMBR202154315_CR52","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.celrep.2013.12.003","volume":"6","author":"P Niewiadomski","year":"2014","unstructured":"Niewiadomski P, Kong JH, Ahrends R, Ma Y, Humke EW, Khan S, Teruel MN, Novitch BG, Rohatgi R (2014) Gli protein activity is controlled by multisite phosphorylation in vertebrate Hedgehog signaling. Cell Rep 6: 168\u2013181","journal-title":"Cell Rep"},{"key":"BFEMBR202154315_CR53","doi-asserted-by":"crossref","first-page":"13320","DOI":"10.1073\/pnas.1822113116","volume":"116","author":"F Omar","year":"2019","unstructured":"Omar F, Findlay JE, Carfray G, Allcock RW, Jiang Z, Moore C, Muir AL, Lannoy M, Fertig BA, Mai D et\u2009al (2019) Small\u2010molecule allosteric activators of PDE4 long form cyclic AMP phosphodiesterases. Proc Natl Acad Sci USA 116: 13320\u201313329","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202154315_CR54","doi-asserted-by":"crossref","first-page":"109519","DOI":"10.1016\/j.cellsig.2019.109519","volume":"69","author":"GJ Pazour","year":"2020","unstructured":"Pazour GJ, Quarmby L, Smith AO, Desai PB, Schmidts M (2020) Cilia in cystic kidney and other diseases. Cell Signal 69: 109519","journal-title":"Cell Signal"},{"key":"BFEMBR202154315_CR55","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0955-0674(02)00012-1","volume":"15","author":"GJ Pazour","year":"2003","unstructured":"Pazour GJ, Witman GB (2003) The vertebrate primary cilium is a sensory organelle. Curr Opin Cell Biol 15: 105\u2013110","journal-title":"Curr Opin Cell Biol"},{"key":"BFEMBR202154315_CR56","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nprot.2014.006","volume":"9","author":"S Picelli","year":"2014","unstructured":"Picelli S, Faridani OR, Bjorklund AK, Winberg G, Sagasser S, Sandberg R (2014) Full\u2010length RNA\u2010seq from single cells using Smart\u2010seq2. Nat Protoc 9: 171\u2013181","journal-title":"Nat Protoc"},{"key":"BFEMBR202154315_CR57","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/bs.mcb.2019.06.001","volume":"153","author":"GA Reif","year":"2019","unstructured":"Reif GA, Wallace DP (2019) ADPKD cell proliferation and Cl(\u2010)\u2010dependent fluid secretion. Methods Cell Biol 153: 69\u201392","journal-title":"Methods Cell Biol"},{"key":"BFEMBR202154315_CR58","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/bs.mcb.2019.04.012","volume":"154","author":"DZ Revell","year":"2019","unstructured":"Revell DZ, Yoder BK (2019) Intravital visualization of the primary cilium, tubule flow, and innate immune cells in the kidney utilizing an abdominal window imaging approach. Methods Cell Biol 154: 67\u201383","journal-title":"Methods Cell Biol"},{"key":"BFEMBR202154315_CR59","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1042\/BST20200757","volume":"49","author":"T Richards","year":"2021","unstructured":"Richards T, Modarage K, Malik SA, Goggolidou P (2021) The cellular pathways and potential therapeutics of Polycystic Kidney Disease. Biochem Soc Trans 49: 1171\u20131188","journal-title":"Biochem Soc Trans"},{"key":"BFEMBR202154315_CR60","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","volume":"11","author":"NE Sanjana","year":"2014","unstructured":"Sanjana NE, Shalem O, Zhang F (2014) Improved vectors and genome\u2010wide libraries for CRISPR screening. Nat Methods 11: 783\u2013784","journal-title":"Nat Methods"},{"key":"BFEMBR202154315_CR81","doi-asserted-by":"publisher","DOI":"10.1101\/2022.06.04.494793","author":"K Sieckmann","year":"2022","unstructured":"Sieckmann K, Winnerling N, Huebecker M, Leyendecker P, Ribeiro D, Gnad T, Pfeifer A, Wachten D (2022) AdipoQ \u2013 a simple, open\u2010source software to quantify adipocyte morphology and function in tissues and in\u00a0vitro. bioRxiv https:\/\/doi.org\/10.1101\/2022.06.04.494793 [PREPRINT]","journal-title":"bioRxiv"},{"key":"BFEMBR202154315_CR61","doi-asserted-by":"crossref","first-page":"5466","DOI":"10.1073\/pnas.0509694103","volume":"103","author":"JM Shillingford","year":"2006","unstructured":"Shillingford JM, Murcia NS, Larson CH, Low SH, Hedgepeth R, Brown N, Flask CA, Novick AC, Goldfarb DA, Kramer\u2010Zucker A et\u2009al (2006) The mTOR pathway is regulated by polycystin\u20101, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci USA 103: 5466\u20135471","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBR202154315_CR62","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/s41588-017-0020-9","volume":"50","author":"JE Siljee","year":"2018","unstructured":"Siljee JE, Wang Y, Bernard AA, Ersoy BA, Zhang S, Marley A, Von Zastrow M, Reiter JF, Vaisse C (2018) Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity. Nat Genet 50: 180\u2013185","journal-title":"Nat Genet"},{"key":"BFEMBR202154315_CR63","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0190430","volume":"13","author":"A Solazzo","year":"2018","unstructured":"Solazzo A, Testa F, Giovanella S, Busutti M, Furci L, Carrera P, Ferrari M, Ligabue G, Mori G, Leonelli M et\u2009al (2018) The prevalence of autosomal dominant polycystic kidney disease (ADPKD): a meta\u2010analysis of European literature and prevalence evaluation in the Italian province of Modena suggest that ADPKD is a rare and underdiagnosed condition. PLoS One 13: e0190430","journal-title":"PLoS One"},{"key":"BFEMBR202154315_CR64","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.devcel.2020.06.034","volume":"54","author":"BN Somatilaka","year":"2020","unstructured":"Somatilaka BN, Hwang SH, Palicharla VR, White KA, Badgandi H, Shelton JM, Mukhopadhyay S (2020) Ankmy2 Prevents smoothened\u2010independent hyperactivation of the hedgehog pathway via cilia\u2010regulated adenylyl cyclase signaling. Dev Cell 54: 710\u2013726.e8","journal-title":"Dev Cell"},{"key":"BFEMBR202154315_CR65","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.7563.1","volume":"4","author":"C Soneson","year":"2015","unstructured":"Soneson C, Love MI, Robinson MD (2015) Differential analyses for RNA\u2010seq: transcript\u2010level estimates improve gene\u2010level inferences. F1000Res 4: 1521","journal-title":"F1000Res"},{"key":"BFEMBR202154315_CR66","doi-asserted-by":"crossref","first-page":"109649","DOI":"10.1016\/j.cellsig.2020.109649","volume":"72","author":"CR Sussman","year":"2020","unstructured":"Sussman CR, Wang X, Chebib FT, Torres VE (2020) Modulation of polycystic kidney disease by G\u2010protein coupled receptors and cyclic AMP signaling. Cell Signal 72: 109649","journal-title":"Cell Signal"},{"key":"BFEMBR202154315_CR67","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1681\/ASN.2004080660","volume":"16","author":"Y Tao","year":"2005","unstructured":"Tao Y, Kim J, Schrier RW, Edelstein CL (2005) Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease. J Am Soc Nephrol 16: 46\u201351","journal-title":"J Am Soc Nephrol"},{"key":"BFEMBR202154315_CR68","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1681\/ASN.2013040398","volume":"25","author":"VE Torres","year":"2014","unstructured":"Torres VE, Harris PC (2014) Strategies targeting cAMP signaling in the treatment of polycystic kidney disease. J Am Soc Nephrol 25: 18\u201332","journal-title":"J Am Soc Nephrol"},{"key":"BFEMBR202154315_CR69","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1016\/j.cell.2021.04.002","volume":"184","author":"ME Truong","year":"2021","unstructured":"Truong ME, Bilekova S, Choksi SP, Li W, Bugaj LJ, Xu K, Reiter JF (2021) Vertebrate cells differentially interpret ciliary and extraciliary cAMP. Cell 184: 2911\u20132926.e18","journal-title":"Cell"},{"key":"BFEMBR202154315_CR70","doi-asserted-by":"crossref","first-page":"107836","DOI":"10.1016\/j.pharmthera.2021.107836","volume":"224","author":"D Wachten","year":"2021","unstructured":"Wachten D, Mick DU (2021) Signal transduction in primary cilia \u2010 analyzing and manipulating GPCR and second messenger signaling. Pharmacol Ther 224: 107836","journal-title":"Pharmacol Ther"},{"key":"BFEMBR202154315_CR71","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.bbadis.2010.11.005","volume":"1812","author":"DP Wallace","year":"2011","unstructured":"Wallace DP (2011) Cyclic AMP\u2010mediated cyst expansion. Biochim Biophys Acta 1812: 1291\u20131300","journal-title":"Biochim Biophys Acta"},{"key":"BFEMBR202154315_CR72","volume":"131","author":"Y Wang","year":"2021","unstructured":"Wang Y, Bernard A, Comblain F, Yue X, Paillart C, Zhang S, Reiter JF, Vaisse C (2021) Melanocortin 4 receptor signals at the neuronal primary cilium to control food intake and body weight. J Clin Invest 131: e142064","journal-title":"J Clin Invest"},{"key":"BFEMBR202154315_CR73","doi-asserted-by":"crossref","first-page":"F897","DOI":"10.1152\/ajprenal.00332.2005","volume":"290","author":"L Warford\u2010Woolgar","year":"2006","unstructured":"Warford\u2010Woolgar L, Peng CY, Shuhyta J, Wakefield A, Sankaran D, Ogborn M, Aukema HM (2006) Selectivity of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD\u2010cy rat kidneys. Am J Physiol Renal Physiol 290: F897\u2013F904","journal-title":"Am J Physiol Renal Physiol"},{"key":"BFEMBR202154315_CR74","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-981-10-2041-4_7","volume":"933","author":"YM Woo","year":"2016","unstructured":"Woo YM, Ko JY, Lee EJ (2016) Validation of effective therapeutic targets for ADPKD using animal models. Adv Exp Med Biol 933: 71\u201384","journal-title":"Adv Exp Med Biol"},{"key":"BFEMBR202154315_CR75","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1101\/gad.348261.121","volume":"35","author":"CT Wu","year":"2021","unstructured":"Wu CT, Hilgendorf KI, Bevacqua RJ, Hang Y, Demeter J, Kim SK, Jackson PK (2021) Discovery of ciliary G protein\u2010coupled receptors regulating pancreatic islet insulin and glucagon secretion. Genes Dev 35: 1243\u20131255","journal-title":"Genes Dev"},{"key":"BFEMBR202154315_CR76","doi-asserted-by":"crossref","first-page":"F677","DOI":"10.1152\/ajprenal.00119.2017","volume":"313","author":"H Ye","year":"2017","unstructured":"Ye H, Wang X, Constans MM, Sussman CR, Chebib FT, Irazabal MV, Young Jr WF, Harris PC, Kirschner LS, Torres VE (2017) The regulatory 1alpha subunit of protein kinase A modulates renal cystogenesis. Am J Physiol Renal Physiol 313: F677\u2013F686","journal-title":"Am J Physiol Renal Physiol"},{"key":"BFEMBR202154315_CR77","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.ejcb.2006.01.002","volume":"85","author":"M Zaccolo","year":"2006","unstructured":"Zaccolo M (2006) Phosphodiesterases and compartmentalized cAMP signalling in the heart. Eur J Cell Biol 85: 693\u2013697","journal-title":"Eur J Cell Biol"},{"key":"BFEMBR202154315_CR78","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1124\/pharmrev.120.000086","volume":"73","author":"M Zaccolo","year":"2021","unstructured":"Zaccolo M, Zerio A, Lobo MJ (2021) Subcellular organization of the cAMP signaling pathway. Pharmacol Rev 73: 278\u2013309","journal-title":"Pharmacol Rev"},{"key":"BFEMBR202154315_CR79","doi-asserted-by":"crossref","first-page":"180","DOI":"10.7150\/ijms.27719","volume":"16","author":"M Zhang","year":"2019","unstructured":"Zhang M, Srichai MB, Zhao M, Chen J, Davis LS, Wu G, Breyer MD, Hao CM (2019) Nonselective cyclooxygenase inhibition retards cyst progression in a murine model of autosomal dominant polycystic kidney disease. Int J Med Sci 16: 180\u2013188","journal-title":"Int J Med Sci"},{"key":"BFEMBR202154315_CR80","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1093\/bioinformatics\/bty895","volume":"35","author":"A Zhu","year":"2019","unstructured":"Zhu A, Ibrahim JG, Love MI (2019) Heavy\u2010tailed prior distributions for sequence count data: removing the noise and preserving large differences. Bioinformatics 35: 2084\u20132092","journal-title":"Bioinformatics"}],"container-title":["The EMBO Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embr.202154315.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/embr.202154315","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/embr.202154315\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/embr.202154315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embr.202154315.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:59:02Z","timestamp":1779112742000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/embr.202154315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,13]]},"references-count":81,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8,3]]}},"alternative-id":["BFEMBR202154315"],"URL":"https:\/\/doi.org\/10.15252\/embr.202154315","relation":{},"ISSN":["1469-221X","1469-3178"],"issn-type":[{"value":"1469-221X","type":"print"},{"value":"1469-3178","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,13]]},"assertion":[{"value":"11 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"DJPH and JI are employees of Mironid Limited.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure and competing interests statement"}}],"article-number":"EMBR202154315"}}