{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:56:20Z","timestamp":1791158180950,"version":"4.1.0"},"reference-count":43,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[1996,4,1]],"date-time":"1996-04-01T00:00:00Z","timestamp":828316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1996,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Hedgehog genes have been implicated in inductive signaling during development in a variety of organisms. A key element of the hedgehog signaling system is encoded by the gene patched. In Drosophila hedgehog regulates gene expression by antagonizing the action of patched. In addition, patched is itself a transcriptional target of hedgehog signaling.<\/jats:p>\n               <jats:p>We have isolated a chicken patched homolog and find it to be strongly expressed adjacent to all tissues where members of the hedgehog family are expressed. As in Drosophila, ectopic expression of Sonic hedgehog leads to ectopic induction of chicken Patched. Based on this regulatory conservation, vertebrate Patched is likely to be directly downstream of Sonic hedgehog signaling.<\/jats:p>\n               <jats:p>An important role of Sonic hedgehog is the regulation of anterior\/posterior pattern in the developing limb bud. Since Patched is directly downstream of the hedgehog signal, the extent of high level Patched expression provides a measure of the distance that Sonic hedgehog diffuses and directly acts. On this basis, we find that Sonic hedgehog directly acts as a signal over only the posterior third of the limb bud.<\/jats:p>\n               <jats:p>During limb patterning, secondary signals are secreted in both the mesoderm (e.g. Bone Morphogenetic Protein-2) and apical ectodermal ridge (e.g. Fibroblast Growth Factor-4) in response to Sonic hedgehog. Thus knowing which is the direct target tissue is essential for unraveling the molecular patterning of the limb. The expression of Patched provides a strong indication that the mesoderm and not the ectoderm is the direct target of Sonic hedgehog signaling in the limb bud.<\/jats:p>\n               <jats:p>Finally we demonstrate that induction of Patched requires Sonic hedgehog but, unlike Bone Morphogenetic Protein-2 and Hox genes, does not require Fibroblast Growth Factor as a co-inducer. It is therefore a more direct target of Sonic hedgehog than previously reported pat-terning genes.<\/jats:p>","DOI":"10.1242\/dev.122.4.1225","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T02:39:03Z","timestamp":1619404743000},"page":"1225-1233","source":"Crossref","is-referenced-by-count":249,"title":["Conservation in <i>hedgehog<\/i> signaling: induction of a chicken <i>patched<\/i> homolog by <i>Sonic hedgehog<\/i> in the developing limb"],"prefix":"10.1242","volume":"122","author":[{"given":"Valeria","family":"Marigo","sequence":"first","affiliation":[{"name":"1 Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Scott","sequence":"additional","affiliation":[{"name":"1 Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA"},{"name":"2 Departments of Developmental Biology and Genetics, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5427, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"2 Departments of Developmental Biology and Genetics, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5427, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa V.","family":"Goodrich","sequence":"additional","affiliation":[{"name":"2 Departments of Developmental Biology and Genetics, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-5427, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford J.","family":"Tabin","sequence":"additional","affiliation":[{"name":"1 Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1996,4,1]]},"reference":[{"key":"2025021322461167600_DEVELOP_122_4_1225C1","volume-title":"Current Protocols in Molecular Biology","author":"Ausubel","year":"1989"},{"key":"2025021322461167600_DEVELOP_122_4_1225C2","doi-asserted-by":"publisher","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":"2025021322461167600_DEVELOP_122_4_1225C3","doi-asserted-by":"publisher","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":"2025021322461167600_DEVELOP_122_4_1225C4","doi-asserted-by":"publisher","first-page":"4459","DOI":"10.1002\/j.1460-2075.1994.tb06768.x","article-title":"Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings","volume":"13","author":"Capdevila","year":"1994","journal-title":"EMBO J"},{"key":"2025021322461167600_DEVELOP_122_4_1225C5","doi-asserted-by":"publisher","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":"2025021322461167600_DEVELOP_122_4_1225C6","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1126\/science.7908145","article-title":"FGF-2: apical ectodermal ridge growth signal for chick limb development","volume":"264","author":"Fallon","year":"1994","journal-title":"Science"},{"key":"2025021322461167600_DEVELOP_122_4_1225C7","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/0092-8674(94)90009-4","article-title":"Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog","volume":"79","author":"Fan","year":"1994","journal-title":"Cell"},{"key":"2025021322461167600_DEVELOP_122_4_1225C8","first-page":"2604","article-title":"Replication-competent retroviral vectors encoding alkaline phosphatase reveal spatial restriction of viral gene expression\/transduction in the chick embryo","volume":"13","author":"Fekete","year":"1993","journal-title":"Mol. 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