{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:46:32Z","timestamp":1791888392191,"version":"4.3.4"},"reference-count":239,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,9,19]],"date-time":"2003-09-19T00:00:00Z","timestamp":1063929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2003,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the hedgehog signaling network, mutations result in various phenotypes, including, among others, holoprosencephaly, nevoid basal cell carcinoma syndrome, Pallister\u2010Hall syndrome, Greig cephalopolysyndactyly, Rubinstein\u2010Taybi syndrome, isolated basal cell carcinoma, and medulloblastoma. Active Hedgehog ligand is double lipid modified with a C\u2010terminal cholesterol moiety and an N\u2010terminal palmitate. Transport active Hedgehog from the signaling cell to the responding cell occurs through three mechanisms: 1). formation of multimeric Hedgehog which makes it soluble; 2). function of Dispatched in releasing the lipid\u2010anchored protein from the signaling cell; and 3). movement across the plasma membrane of the responding cell by Tout\u2010velu\u2010dependent synthesis of heparan sulfate proteoglycan. In the responding cell, active Hedgehog binds to its receptor Patched, a 12\u2010pass transmembrane protein, which frees Smoothened, an adjacent 7\u2010pass transmembrane protein, for downstream signaling. Patched and Smoothened may shuttle oppositely between the plasma membrane and endocytic vesicles in response to active Hedgehog ligand. In downstream signaling, Cubitus interruptus (Gli proteins in vertebrates), Costal 2, Fused, and Suppressor of Fused form a tetrameric complex. Cubitus interruptus is a bifunctional transcription regulator. In the absence of active Hedgehog ligand, a truncated transcriptional repressor is generated that binds target genes and blocks their transcription. In the presence of active Hedgehog ligand, a full length transcriptional activator binds target genes and upregulates their transcription. Target genes include <jats:italic>Wingless<\/jats:italic> (<jats:italic>Wnt<\/jats:italic> gene family in vertebrates), <jats:italic>Decapentaplegic<\/jats:italic> (Bone Morphogenetic Proteins in vertebrates), and <jats:italic>Patched<\/jats:italic>. The upregulation of Patched expression, resulting in Patched protein at the cell membrane, sequesters Hedgehog and limits its spread beyond the cells in which it is produced. Thus, a balance is created by the antagonism of Hedgehog and Patched, whose relative concentrations alternate with respect to each other. Many more factors that are essential for the hedgehog signaling network are also discussed: Megalin, Rab23, Hip, GAS1, PKA, GSK3, CK1, Slimb, SAP18, and CBP. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.20495","type":"journal-article","created":{"date-parts":[[2003,10,7]],"date-time":"2003-10-07T08:03:09Z","timestamp":1065513789000},"page":"5-28","source":"Crossref","is-referenced-by-count":327,"title":["The hedgehog signaling network"],"prefix":"10.1002","volume":"123A","author":[{"suffix":"Jr.","given":"M. Michael","family":"Cohen,","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,9,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162356199"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202080"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/386735a0"},{"key":"e_1_2_6_5_1","first-page":"1260","article-title":"Deletion mapping of gliomas suggests the presence of two small regions for candiate tumor\u2010suppressor genes in a 17\u2010cM interval on chromosome 10q","volume":"58","author":"Albarosa R","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80094-X"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00044-7"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.24.5119"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.5.1555-1566.2002"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80292-5"},{"key":"e_1_2_6_11_1","first-page":"4293","article-title":"Expression of the vertebrate Gli proteins in Drosophila reveals a distribution of activator and repressor activities","volume":"127","author":"Aza\u2010Blanc P","year":"2000","journal-title":"Development"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.3.022502.103031"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-176-41842"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.9.2214"},{"key":"e_1_2_6_15_1","first-page":"191","article-title":"Multiple roles of cholesterol in hedgehog protein biogenesis and signaling","author":"Beachy PA","year":"1997","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.2950110309"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/27932"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-353"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073733"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-259"},{"key":"e_1_2_6_21_1","first-page":"1164","article-title":"A congenital cyclopian\u2010type malformation in lambs induced by maternal ingestion of a range plant, Veratrum californicum","volume":"24","author":"Binns W","year":"1963","journal-title":"Am J Vet Res"},{"key":"e_1_2_6_22_1","first-page":"839","article-title":"Chronologic evaluation of teratogenicity in sheep fed Veratrum californicum","volume":"147","author":"Binns W","year":"1965","journal-title":"J Am Vet Med Assoc"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00480-3"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000103)90:1<29::AID-AJMG6>3.0.CO;2-Z"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/31242"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00271-4"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/2484"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.8.791"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420080104"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81677-3"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5396.2012"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120.4.987"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13630"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1064437"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80067-2"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082096999"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81374-4"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.24.4943"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81960-1"},{"key":"e_1_2_6_40_1","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1242\/dev.126.16.3607","article-title":"Mutants of cubitus interruptus that are independent of PKA regulation are independent of hedgehog signaling","volume":"126","author":"Chen Y","year":"1999","journal-title":"Development"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0346"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/365855a0"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/17611"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0020.1999.283280314.x"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10289"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10750"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10258"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5369.1603"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100249900004"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(97)01275-4"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/39918"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.12.8143"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/35083601"},{"key":"e_1_2_6_55_1","first-page":"165","article-title":"Altered cholesterol biosynthesis in rats: a model for Smith\u2010Lemli\u2010Opitz syndrome","volume":"51","author":"Dehart DB","year":"1995","journal-title":"Teratology"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0709-3"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90429-G"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.5.1848"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.12.7152"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00056-8"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513819209023323"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00375-0"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/35084089"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00200-2"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10642"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(97)01377-2"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105871200"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0996-78"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng577"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.16.9572"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19991126)87:3<207::AID-AJMG3>3.0.CO;2-5"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5329.1109"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/73417"},{"key":"e_1_2_6_74_1","first-page":"4800","article-title":"Loss of the chromosomal region 10q23\u201025 in prostate cancer","volume":"55","author":"Gray IC","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/76074"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120.11.3119"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.21.12125"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81268-4"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0598-619"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001099900018"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(96)10051-2"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1997.8589"},{"key":"e_1_2_6_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(02)00290-8"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90021-4"},{"key":"e_1_2_6_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0393-241"},{"key":"e_1_2_6_86_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1994.1097"},{"key":"e_1_2_6_87_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.18.3553"},{"key":"e_1_2_6_88_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9775"},{"key":"e_1_2_6_89_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.220251997"},{"key":"e_1_2_6_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00895-3"},{"key":"e_1_2_6_91_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.938601"},{"key":"e_1_2_6_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00755-7"},{"key":"e_1_2_6_93_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10004"},{"key":"e_1_2_6_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature733"},{"key":"e_1_2_6_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/35154"},{"key":"e_1_2_6_96_1","first-page":"543","article-title":"Extra\u2010toes: a new mutant gene causing multiple abnormalities in the mouse","volume":"17","author":"Johnson DR","year":"1967","journal-title":"J Embrol Exper Morphol"},{"key":"e_1_2_6_97_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300002962"},{"key":"e_1_2_6_98_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5268.1668"},{"key":"e_1_2_6_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00045-9"},{"key":"e_1_2_6_100_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0524"},{"key":"e_1_2_6_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00129-X"},{"key":"e_1_2_6_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(01)00295-2"},{"key":"e_1_2_6_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0397-266"},{"key":"e_1_2_6_104_1","doi-asserted-by":"publisher","DOI":"10.1159\/000064057"},{"key":"e_1_2_6_105_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010832200"},{"key":"e_1_2_6_106_1","doi-asserted-by":"publisher","DOI":"10.1159\/000134207"},{"key":"e_1_2_6_107_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420030210"},{"key":"e_1_2_6_108_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-149-38794"},{"key":"e_1_2_6_109_1","doi-asserted-by":"publisher","DOI":"10.1139\/o66-101"},{"key":"e_1_2_6_110_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420010103"},{"key":"e_1_2_6_111_1","first-page":"1","article-title":"Inborn errors of cholesterol biosynthesis","volume":"47","author":"Kelley RI","year":"2000","journal-title":"Adv Pediatr"},{"key":"e_1_2_6_112_1","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2001.20722"},{"key":"e_1_2_6_113_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080190"},{"key":"e_1_2_6_114_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.2.634"},{"key":"e_1_2_6_115_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3563490"},{"key":"e_1_2_6_116_1","doi-asserted-by":"publisher","DOI":"10.1038\/332371a0"},{"key":"e_1_2_6_117_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2000-1-5-reviews3002"},{"key":"e_1_2_6_118_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.20.13933"},{"key":"e_1_2_6_119_1","first-page":"2247","article-title":"Basal\u2010cell nevomatosis associated with multifocal fetal rhabdomyoma. A case","volume":"17","author":"Klijanienko J","year":"1988","journal-title":"Presse M\u00e9d"},{"key":"e_1_2_6_120_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01272"},{"key":"e_1_2_6_121_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199609)54:3<115::AID-TERA1>3.0.CO;2-2"},{"key":"e_1_2_6_122_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199709)56:3<188::AID-TERA2>3.0.CO;2-Y"},{"key":"e_1_2_6_123_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000773200"},{"key":"e_1_2_6_124_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5345.1947"},{"key":"e_1_2_6_125_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(02)02640-9"},{"key":"e_1_2_6_126_1","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1101\/gad.14.15.1933","article-title":"A C. elegans patched gene, ptc\u20101 functions in germ\u2010line cytokinesis","volume":"14","author":"Kuwabara PE","year":"2000","journal-title":"Genes Dev"},{"key":"e_1_2_6_127_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)02028-X"},{"key":"e_1_2_6_128_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202360"},{"key":"e_1_2_6_129_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971128)73:1<24::AID-AJMG6>3.0.CO;2-P"},{"key":"e_1_2_6_130_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.663"},{"key":"e_1_2_6_131_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00323-2"},{"key":"e_1_2_6_132_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.201418298"},{"key":"e_1_2_6_133_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050541"},{"key":"e_1_2_6_134_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00369-5"},{"key":"e_1_2_6_135_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.41.26265"},{"key":"e_1_2_6_136_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01033"},{"key":"e_1_2_6_137_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00977-7"},{"key":"e_1_2_6_138_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199803)21:3<276::AID-GCC15>3.0.CO;2-N"},{"key":"e_1_2_6_139_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(02)02400-5"},{"key":"e_1_2_6_140_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206743200"},{"key":"e_1_2_6_141_1","doi-asserted-by":"publisher","DOI":"10.1038\/384176a0"},{"key":"e_1_2_6_142_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00178-6"},{"key":"e_1_2_6_143_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(98)00050-0"},{"key":"e_1_2_6_144_1","doi-asserted-by":"publisher","DOI":"10.1016\/0962-8924(94)90202-X"},{"key":"e_1_2_6_145_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.15.2759"},{"key":"e_1_2_6_146_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0454"},{"key":"e_1_2_6_147_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-001-2115-X"},{"key":"e_1_2_6_148_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201933200"},{"key":"e_1_2_6_149_1","doi-asserted-by":"publisher","DOI":"10.1038\/514"},{"key":"e_1_2_6_150_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.4.843"},{"key":"e_1_2_6_151_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203245"},{"key":"e_1_2_6_152_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0695-5"},{"key":"e_1_2_6_153_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.1.113"},{"key":"e_1_2_6_154_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70227-1"},{"key":"e_1_2_6_155_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-2-4"},{"key":"e_1_2_6_156_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(97)01093-7"},{"key":"e_1_2_6_157_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-104"},{"key":"e_1_2_6_158_1","first-page":"6203","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Muenke M","year":"2001"},{"key":"e_1_2_6_159_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(02)02405-4"},{"key":"e_1_2_6_160_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80018-9"},{"key":"e_1_2_6_161_1","doi-asserted-by":"publisher","DOI":"10.1038\/35010610"},{"key":"e_1_2_6_162_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.13.2479"},{"key":"e_1_2_6_163_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.7.3438"},{"key":"e_1_2_6_164_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(98)01634-5"},{"key":"e_1_2_6_165_1","doi-asserted-by":"publisher","DOI":"10.1038\/287795a0"},{"key":"e_1_2_6_166_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(02)00333-7"},{"key":"e_1_2_6_167_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110730200"},{"key":"e_1_2_6_168_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.3.387"},{"key":"e_1_2_6_169_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.4.6.1053"},{"key":"e_1_2_6_170_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5313.817"},{"key":"e_1_2_6_171_1","unstructured":"OuspenskaiaMV KarkeraJD RoesslerE ShenMM GoldmuntsE BowersP TowbinJ BelmontJ MuenkeM.2002.Role ofFAST1gene in the development of holoprosencephaly (HPE) and congenital cardiac malformations in humans. American Society of Human Genetics 52nd Annual Meeting October 15\u201019 Baltimore Maryland Abstract No. 822 p. 313."},{"key":"e_1_2_6_172_1","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1242\/dev.127.8.1593","article-title":"Mouse Gli1mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation","volume":"127","author":"Park HL","year":"2000","journal-title":"Development"},{"key":"e_1_2_6_173_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(98)01473-5"},{"key":"e_1_2_6_174_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9335"},{"key":"e_1_2_6_175_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5399"},{"key":"e_1_2_6_176_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.14037"},{"key":"e_1_2_6_177_1","doi-asserted-by":"publisher","DOI":"10.1038\/376348a0"},{"key":"e_1_2_6_178_1","unstructured":"Phenylthiocarbamide (PTC). OMIM 171200."},{"key":"e_1_2_6_179_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.01301.x"},{"key":"e_1_2_6_180_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(99)01854-5"},{"key":"e_1_2_6_181_1","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1242\/dev.110.4.1153","article-title":"Evidence for allelism of the recessive insertional mutation add and the dominant mouse mutation extra toes (Xt)","volume":"110","author":"Pohl TP","year":"1990","journal-title":"Development"},{"key":"e_1_2_6_182_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80074-4"},{"key":"e_1_2_6_183_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/132.3.725"},{"key":"e_1_2_6_184_1","doi-asserted-by":"publisher","DOI":"10.1038\/347087a0"},{"key":"e_1_2_6_185_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00664-5"},{"key":"e_1_2_6_186_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(89)80188-3"},{"key":"e_1_2_6_187_1","first-page":"842","article-title":"Sporadic medulloblastomas contain PTCH mutations","volume":"57","author":"Raffel C","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_6_188_1","first-page":"2243","article-title":"Chromosome 10 deletion mapping in human gliomas: a common deletion region in 10q25","volume":"10","author":"Rasheed BK","year":"1995","journal-title":"Oncogene"},{"key":"e_1_2_6_189_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(96)10031-1"},{"key":"e_1_2_6_190_1","first-page":"5141","article-title":"Refined mapping of 12q13\u2010q15 amplicons in human malignant gliomas suggests CDK4\/SAS and MDM2 as independent amplification targets","volume":"56","author":"Reifenberger G","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_6_191_1","first-page":"1798","article-title":"Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system","volume":"58","author":"Reifenberger J","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_192_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80331-1"},{"key":"e_1_2_6_193_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg058"},{"key":"e_1_2_6_194_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-357"},{"key":"e_1_2_6_195_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.11.1847"},{"key":"e_1_2_6_196_1","unstructured":"RoesslerE DuY MullorJL CasasE AllenWP EllisI Gillessen\u2010KaesbachG RoederE MingJE Ruiz i AltabaA MuenkeM.2002.Loss\u2010of\u2010function mutations in the humanGLI2gene cause holoprosencephaly and familial pan\u2010hypopituitarism. American Society of Human Genetics 52ndAnnual Meeting October 15\u201019 Baltimore Maryland Abstract No. 132 p. 190."},{"key":"e_1_2_6_197_1","first-page":"451","article-title":"Action teratogenie du triparanol chez l'animal","volume":"21","author":"Roux C","year":"1964","journal-title":"Arch Fran\u00e7 P\u00e9diatr"},{"key":"e_1_2_6_198_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80325-6"},{"key":"e_1_2_6_199_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(99)01840-5"},{"key":"e_1_2_6_200_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc796"},{"key":"e_1_2_6_201_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.8.8.3104"},{"key":"e_1_2_6_202_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.10.5408"},{"key":"e_1_2_6_203_1","first-page":"5L384","article-title":"The mouse mutant polydactyly Nagoya (Pdn) defines a novel allele of the zinc finger gene Gli3","author":"Schimmang T","year":"1994","journal-title":"Mamm Genome"},{"key":"e_1_2_6_204_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.12.2155"},{"key":"e_1_2_6_205_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.2.291"},{"key":"e_1_2_6_206_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.3.284"},{"key":"e_1_2_6_207_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.16.2072"},{"key":"e_1_2_6_208_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)02004-4"},{"key":"e_1_2_6_209_1","doi-asserted-by":"publisher","DOI":"10.1038\/384129a0"},{"key":"e_1_2_6_210_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.112.23.4437"},{"key":"e_1_2_6_211_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00179-8"},{"key":"e_1_2_6_212_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(97)01159-8"},{"key":"e_1_2_6_213_1","doi-asserted-by":"publisher","DOI":"10.1038\/35077219"},{"key":"e_1_2_6_214_1","doi-asserted-by":"publisher","DOI":"10.1038\/35023008"},{"key":"e_1_2_6_215_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00989"},{"key":"e_1_2_6_216_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng916"},{"key":"e_1_2_6_217_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80214-2"},{"key":"e_1_2_6_218_1","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.1242\/dev.126.18.4039","article-title":"Differential requirements of the Fused kinase for Hedgehog signaling in the Drosophila embryo","volume":"126","author":"Th\u00e9rond PP","year":"1999","journal-title":"Development"},{"key":"e_1_2_6_219_1","doi-asserted-by":"publisher","DOI":"10.1038\/382547a0"},{"key":"e_1_2_6_220_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9297(07)62934-6"},{"key":"e_1_2_6_221_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201340"},{"key":"e_1_2_6_222_1","first-page":"4677","article-title":"Trichoepitheliomas contain somatic mutations in the overexpressed PTC gene: support for a gatekeeper mechanism in skin tumorigenesis","volume":"57","author":"Vorechovsky I","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_6_223_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.613"},{"key":"e_1_2_6_224_1","doi-asserted-by":"publisher","DOI":"10.1038\/9718"},{"key":"e_1_2_6_225_1","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1242\/dev.126.22.5097","article-title":"The subcellular localization and activity of Drosophila cubitus interruptus are regulated at multiple levels","volume":"126","author":"Wang QT","year":"1999","journal-title":"Development"},{"key":"e_1_2_6_226_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80678-9"},{"key":"e_1_2_6_227_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.843900"},{"key":"e_1_2_6_228_1","doi-asserted-by":"publisher","DOI":"10.1086\/301936"},{"key":"e_1_2_6_229_1","first-page":"21","article-title":"Most germ\u2010line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype\u2010phenotype correlations are evident","volume":"60","author":"Wicking C","year":"1997","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_230_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201644"},{"key":"e_1_2_6_231_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.11.1979"},{"key":"e_1_2_6_232_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8460"},{"key":"e_1_2_6_233_1","doi-asserted-by":"publisher","DOI":"10.1086\/302760"},{"key":"e_1_2_6_234_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80329-3"},{"key":"e_1_2_6_235_1","first-page":"2581","article-title":"Mutations in the human homologue of Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system","volume":"57","author":"Wolter M","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_6_236_1","first-page":"2369","article-title":"Mutations of the Patched gene in several types of sporadic extracutaneous tumors","volume":"57","author":"Xie J","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_6_237_1","doi-asserted-by":"publisher","DOI":"10.1038\/34201"},{"key":"e_1_2_6_238_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.9.1385"},{"key":"e_1_2_6_239_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(96)20014-9"},{"key":"e_1_2_6_240_1","doi-asserted-by":"publisher","DOI":"10.1038\/35079648"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.20495","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.20495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T20:14:19Z","timestamp":1694636059000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.20495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9,19]]},"references-count":239,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,11,15]]}},"alternative-id":["10.1002\/ajmg.a.20495"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.20495","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9,19]]}}}