{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:32:01Z","timestamp":1774085521577,"version":"3.50.1"},"reference-count":52,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,7,17]],"date-time":"2013-07-17T00:00:00Z","timestamp":1374019200000},"content-version":"vor","delay-in-days":5311,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Biology"],"published-print":{"date-parts":[[1999,1]]},"DOI":"10.1016\/s0960-9822(99)80018-9","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T15:05:09Z","timestamp":1027609509000},"page":"76-84","source":"Crossref","is-referenced-by-count":261,"title":["Sonic hedgehog signaling by the Patched\u2013Smoothened receptor complex"],"prefix":"10.1016","volume":"9","author":[{"given":"Maximilien","family":"Murone","sequence":"first","affiliation":[]},{"given":"Arnon","family":"Rosenthal","sequence":"additional","affiliation":[]},{"given":"Frederic J.","family":"de Sauvage","sequence":"additional","affiliation":[]}],"member":"78","reference":[{"key":"10.1016\/S0960-9822(99)80018-9_BIB1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/287795a0","article-title":"Mutations affecting segment number and polarity in Drosophila","volume":"287","author":"Nusslein-Volhard","year":"1980","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0168-9525(96)10051-2","article-title":"The world according to hedgehog","volume":"13","author":"Hammerschmidt","year":"1997","journal-title":"Trends Genet"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB3","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/0092-8674(93)90627-3","article-title":"Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity","volume":"75","author":"Echelard","year":"1993","journal-title":"Cell"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB4","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1016\/0092-8674(93)90628-4","article-title":"A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos","volume":"75","author":"Krauss","year":"1993","journal-title":"Cell"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB5","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/S0960-9822(95)00185-0","article-title":"Patterning activities of vertebrate hedgehog proteins in the developing eye and brain","volume":"5","author":"Ekker","year":"1995","journal-title":"Curr Biol"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB6","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S0955-0674(97)80092-0","article-title":"Differentiation of the vertebrate neural tube","volume":"9","author":"Bronner-Fraser","year":"1997","journal-title":"Curr Opin Cell Biol"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB7","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/S0960-9822(95)00123-0","article-title":"Somite differentiation. Sonic signals somites","volume":"5","author":"Bumcrot","year":"1995","journal-title":"Curr Biol"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB8","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/0092-8674(93)90626-2","article-title":"Sonic hedgehog mediates the polarizing activity of the ZPA","volume":"75","author":"Riddle","year":"1993","journal-title":"Cell"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB9","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1242\/dev.121.10.3163","article-title":"Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut","volume":"121","author":"Roberts","year":"1995","journal-title":"Development"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB10","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/382547a0","article-title":"smoothened encodes a receptor-like serpentine protein required for hedgehog signalling","volume":"382","author":"van den Heuvel","year":"1996","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB11","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0092-8674(00)80094-X","article-title":"The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal","volume":"86","author":"Alcedo","year":"1996","journal-title":"Cell"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB12","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/384129a0","article-title":"The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog","volume":"384","author":"Stone","year":"1996","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB13","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/0092-8674(89)90021-4","article-title":"The Drosophila patched gene encodes a putative membrane protein required for segmental patterning","volume":"59","author":"Hooper","year":"1989","journal-title":"Cell"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB14","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/341508a0","article-title":"A protein with several possible membrane-spanning domains encoded by the Drosophila segment polarity gene patched","volume":"341","author":"Nakano","year":"1989","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB15","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/353184a0","article-title":"Role of the Drosophila patched gene in positional signalling","volume":"353","author":"Ingham","year":"1991","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB16","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/368208a0","article-title":"Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein","volume":"368","author":"Basler","year":"1994","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/j.1460-2075.1994.tb06236.x","article-title":"The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development","volume":"13","author":"Capdevila","year":"1994","journal-title":"EMBO J"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB18","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/384176a0","article-title":"Biochemical evidence that patched is the Hedgehog receptor","volume":"384","author":"Marigo","year":"1996","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB19","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1126\/science.272.5268.1668","article-title":"Human homolog of patched, a candidate gene for the basal cell nevus syndrome","volume":"272","author":"Johnson","year":"1996","journal-title":"Science"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB20","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0092-8674(00)81268-4","article-title":"Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome","volume":"85","author":"Hahn","year":"1996","journal-title":"Cell"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB21","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/ng0996-78","article-title":"The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas","volume":"14","author":"Gailani","year":"1996","journal-title":"Nat Genetics"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/34201","article-title":"Activating Smoothened mutations in sporadic basal-cell carcinoma","volume":"391","author":"Xie","year":"1998","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB23","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1126\/science.3563490","article-title":"Identification of an amplified, highly expressed gene in a human glioma","volume":"236","author":"Kinzler","year":"1987","journal-title":"Science"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB24","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/332371a0","article-title":"The GLI gene is a member of the Kruppel family of zinc finger proteins","volume":"332","author":"Kinzler","year":"1988","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB25","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1126\/science.272.5268.1621","article-title":"Sending and receiving the hedgehog signal: control by the Drosophila Gli protein Cubitus interruptus","volume":"272","author":"Dominguez","year":"1996","journal-title":"Science"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB26","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1101\/gad.10.16.2003","article-title":"Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins","volume":"10","author":"Alexandre","year":"1996","journal-title":"Genes Dev"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0896-6273(00)80344-X","article-title":"Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1","volume":"19","author":"Hynes","year":"1997","journal-title":"Neuron"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB28","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1073\/pnas.94.6.2404","article-title":"Hedgehog signaling regulates transcription through cubitus interruptus, a sequence-specific DNA binding protein","volume":"94","author":"Von Ohlen","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB29","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1242\/dev.125.12.2203","article-title":"Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog","volume":"125","author":"Altaba","year":"1998","journal-title":"Development"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB30","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1242\/dev.124.13.2537","article-title":"Gli1 is a target of Sonic hedgehog that induces ventral neural tube development","volume":"124","author":"Lee","year":"1997","journal-title":"Development"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB31","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/dbio.1996.0300","article-title":"Sonic hedgehog differentially regulates expression of GLI and GLI3 during limb development","volume":"180","author":"Marigo","year":"1996","journal-title":"Dev Biol"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB32","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/39918","article-title":"Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours","volume":"389","author":"Dahmane","year":"1997","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB33","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1093\/emboj\/17.13.3505","article-title":"Transducing Hedgehog: the story so far","volume":"17","author":"Ingham","year":"1998","journal-title":"EMBO J"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB34","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0014-5793(97)00014-8","article-title":"Fibroblasts expressing Sonic hedgehog induce osteoblast differentiation and ectopic bone formation","volume":"404","author":"Kinto","year":"1997","journal-title":"FEBS Lett"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB35","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1242\/dev.124.7.1313","article-title":"A binding site for Gli proteins is essential for HNF-3beta floor plate enhancer activity in transgenics and can respond to Shh in vitro","volume":"124","author":"Sasaki","year":"1997","journal-title":"Development"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB36","doi-asserted-by":"crossref","first-page":"18968","DOI":"10.1016\/S0021-9258(17)32261-5","article-title":"Chimeric muscarinic cholinergic:beta-adrenergic receptors that are functionally promiscuous among G proteins","volume":"269","author":"Wong","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB37","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1242\/dev.110.1.291","article-title":"Cell patterning in the Drosophila segment: spatial regulation of the segment polarity gene patched","volume":"110","author":"Hidalgo","year":"1990","journal-title":"Development"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB38","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1101\/gad.10.3.301","article-title":"Conservation of the hedgehog\/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog","volume":"10","author":"Goodrich","year":"1996","journal-title":"Genes Dev"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB39","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0092-8674(00)81374-4","article-title":"Dual roles for patched in sequestering and transducing Hedgehog","volume":"87","author":"Chen","year":"1996","journal-title":"Cell"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB40","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1101\/SQB.1997.062.01.027","article-title":"The smoothened gene and hedgehog signal transduction in Drosophila and vertebrate development","volume":"62","author":"Quirk","year":"1997","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB41","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/37138","article-title":"Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling","volume":"390","author":"Slusarski","year":"1997","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB42","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1096\/fasebj.9.9.7601339","article-title":"The family of G-protein- coupled receptors","volume":"9","author":"Strader","year":"1995","journal-title":"FASEB J"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB43","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/0092-8674(95)90508-1","article-title":"cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in Drosophila imaginal discs","volume":"80","author":"Pan","year":"1995","journal-title":"Cell"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB44","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/0092-8674(95)90509-X","article-title":"Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development","volume":"80","author":"Li","year":"1995","journal-title":"Cell"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB45","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1101\/gad.10.6.647","article-title":"Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo","volume":"10","author":"Hammerschmidt","year":"1996","journal-title":"Genes Dev"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB46","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1073\/pnas.95.5.2349","article-title":"Protein kinase A directly regulates the activity and proteolysis of cubitus interruptus","volume":"95","author":"Chen","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BFb0031030","article-title":"Complexity and versatility of the transcriptional response to cAMP","volume":"124","author":"Delmas","year":"1994","journal-title":"Rev Physiol Biochem Pharmacol"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB48","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/386735a0","article-title":"Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signalling","volume":"386","author":"Akimaru","year":"1997","journal-title":"Nature"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB49","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1101\/gad.11.17.2250","article-title":"Dual pathways for induction of wingless expression by protein kinase A and Hedgehog in Drosophila embryos","volume":"11","author":"Ohlmeyer","year":"1997","journal-title":"Genes Dev"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB50","first-page":"G586","article-title":"Turning off the signal: mechanisms that attenuate signaling by G protein-coupled receptors","volume":"273","author":"Grady","year":"1997","journal-title":"Am J Physiol"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB51","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1126\/science.3014647","article-title":"Neutralization of the AIDS retrovirus by antibodies to a recombinant envelope glycoprotein","volume":"233","author":"Lasky","year":"1986","journal-title":"Science"},{"key":"10.1016\/S0960-9822(99)80018-9_BIB52","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1677\/jme.0.0180077","article-title":"Cloning and characterization of a human leptin receptor using a biologically active leptin immunoadhesin","volume":"18","author":"Luoh","year":"1997","journal-title":"J Mol Endocrinol"}],"container-title":["Current Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960982299800189?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960982299800189?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T02:20:13Z","timestamp":1620613213000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960982299800189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,1]]},"references-count":52,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1999,1]]}},"alternative-id":["S0960982299800189"],"URL":"https:\/\/doi.org\/10.1016\/s0960-9822(99)80018-9","relation":{},"ISSN":["0960-9822"],"issn-type":[{"value":"0960-9822","type":"print"}],"subject":[],"published":{"date-parts":[[1999,1]]}}}