{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:54:25Z","timestamp":1791071665040,"version":"4.1.0"},"reference-count":114,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,5,26]],"date-time":"2014-05-26T00:00:00Z","timestamp":1401062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001463","name":"American Society of Nephrology","doi-asserted-by":"crossref","award":["Gottschalk Research Scholar Award"],"award-info":[{"award-number":["Gottschalk Research Scholar Award"]}],"id":[{"id":"10.13039\/100001463","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["R21DK088048"],"award-info":[{"award-number":["R21DK088048"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIDDK (to Xiaogang Li)","award":["R01DK084097"],"award-info":[{"award-number":["R01DK084097"]}]},{"name":"NIGM (PI: Dale Abrahamson)","award":["P20GM104936"],"award-info":[{"award-number":["P20GM104936"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt C"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p>For more than a decade, evidence has accumulated linking dysfunction of primary cilia to renal cystogenesis, yet molecular mechanisms remain undefined. The pathogenesis of renal cysts is complex, involving multiple cellular aberrations and signaling pathways. Adding to this complexity, primary cilia exhibit multiple roles in a context\u2010dependent manner. On renal epithelial cells, primary cilia act as mechanosensors and trigger extracellular Ca<jats:sup>2+<\/jats:sup> influx in response to laminar fluid flow. During mammalian development, primary cilia mediate the Hedgehog (Hh), Wnt, and Notch pathways, which control cell proliferation and differentiation, and tissue morphogenesis. Further, experimental evidence suggests the developmental state of the kidney strongly influences renal cystic disease. Thus, we review evidence for regulation of Ca<jats:sup>2+<\/jats:sup> and cAMP, key molecules in renal cystogenesis, at the primary cilium, the role of Hh, Wnt, and Notch signaling in renal cystic disease, and the interplay between these developmental pathways and Ca<jats:sup>2+<\/jats:sup> signaling. Indeed if these developmental pathways influence renal cystogenesis, these may represent novel therapeutic targets that can be integrated into a combination therapy for renal cystic disease. <jats:bold>Birth Defects Research (Part C) 102:159\u2013173, 2014.<\/jats:bold> \u00a9 <jats:bold>2014 Wiley Periodicals, Inc.<\/jats:bold><\/jats:p>","DOI":"10.1002\/bdrc.21065","type":"journal-article","created":{"date-parts":[[2014,5,26]],"date-time":"2014-05-26T12:38:21Z","timestamp":1401107901000},"page":"159-173","source":"Crossref","is-referenced-by-count":24,"title":["Developmental signaling: Does it bridge the gap between cilia dysfunction and renal cystogenesis?"],"prefix":"10.1002","volume":"102","author":[{"given":"Pamela V.","family":"Tran","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology University of Kansas Medical Center Kansas City Kansas"},{"name":"The Kidney Institute, University of Kansas Medical Center Kansas City Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhulika","family":"Sharma","sequence":"additional","affiliation":[{"name":"The Kidney Institute, University of Kansas Medical Center Kansas City Kansas"},{"name":"Department of Internal Medicine University of Kansas Medical Center Kansas City Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Li","sequence":"additional","affiliation":[{"name":"The Kidney Institute, University of Kansas Medical Center Kansas City Kansas"},{"name":"Department of Internal Medicine University of Kansas Medical Center Kansas City Kansas"},{"name":"Department of Biochemistry and Molecular Biology University of Kansas Medical Center Kansas City Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Calvet","sequence":"additional","affiliation":[{"name":"The Kidney Institute, University of Kansas Medical Center Kansas City Kansas"},{"name":"Department of Biochemistry and Molecular Biology University of Kansas Medical Center Kansas City Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2072"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018217108"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00843.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43025"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.02.036"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-010-1704-x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05651207"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/snep.2001.20929"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3658"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00574.2009"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000334166"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016214108"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04117"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1670"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12832"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12833"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.23.4655"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.23.090506.123249"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.05.030"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.296"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1701"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2011.109"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2020"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp190"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0010053"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64313"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.127308"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02220"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505328102"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02061"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1902910"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2984"},{"key":"e_1_2_8_34_1","article-title":"Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli","author":"Jin X","year":"2013","journal-title":"Cell Mol Life Sci"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200808137"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011080829"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.400"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.04.009"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009030271"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912180106"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1399-9"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200805124"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp588"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt081"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2010"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2259"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt054"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr339"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2452"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0836980100"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00173"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02806"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01894"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.054452"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010010127"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2715"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012050490"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1086\/505332"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(08)00812-0"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)94014-0"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.56"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.01016.x"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00362.2007"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1076"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.12.003"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1731"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009060603"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2013.04.008"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012050526"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1052-z"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn045"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1675"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02011114"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-001-0075-4"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-002-1042-4"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410697200"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011410108"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011030277"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(08)00605-4"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.5.1825-1835.2000"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr013"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139740"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204825"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.179"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.050377"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32833dbc31"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.037408"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1552"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006020136"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp165"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.08.023"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2647"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.534"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009090925"},{"key":"e_1_2_8_95_1","first-page":"89","article-title":"The hedgehog pathway inhibitor GDC\u20100449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin\u2010resistant lung cancer cells","volume":"32","author":"Tian F","year":"2012","journal-title":"Anticancer Res"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205511"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0070"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1004"},{"key":"e_1_2_8_99_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.105"},{"key":"e_1_2_8_100_1","author":"Tran PV","year":"2014","journal-title":"Downregulating Hedgehog signaling reduces renal cystogenic potential of mouse models J Am Soc Nephrol"},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.11.005"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80678-9"},{"key":"e_1_2_8_103_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007060688"},{"key":"e_1_2_8_104_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00072-07"},{"key":"e_1_2_8_105_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01089-09"},{"key":"e_1_2_8_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.02.015"},{"key":"e_1_2_8_107_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2011"},{"key":"e_1_2_8_108_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.049437"},{"key":"e_1_2_8_109_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005060645"},{"key":"e_1_2_8_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(97)90496-0"},{"key":"e_1_2_8_111_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405079200"},{"key":"e_1_2_8_112_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012050442"},{"key":"e_1_2_8_113_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100621"},{"key":"e_1_2_8_114_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt556"},{"key":"e_1_2_8_115_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64401"}],"container-title":["Birth Defects Research Part C: Embryo Today: Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdrc.21065","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdrc.21065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T00:31:54Z","timestamp":1696638714000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdrc.21065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,26]]},"references-count":114,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1002\/bdrc.21065"],"URL":"https:\/\/doi.org\/10.1002\/bdrc.21065","archive":["Portico"],"relation":{},"ISSN":["1542-975X","1542-9768"],"issn-type":[{"value":"1542-975X","type":"print"},{"value":"1542-9768","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,26]]}}}