{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:16:42Z","timestamp":1790457402277,"version":"4.1.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,3,23]]},"abstract":"<jats:p>\n                    Expression of Sonic Hedgehog (\n                    <jats:italic>Shh<\/jats:italic>\n                    ) in the posterior mesenchyme of the developing limb bud regulates patterning and growth of the developing limb by activation of the Hedgehog (Hh) signaling pathway. Through the analysis of\n                    <jats:italic>Shh<\/jats:italic>\n                    and Hh signaling target genes, it has been shown that activation in the limb bud mesoderm is required for normal limb development to occur. In contrast, it has been stated that Hh signaling in the limb bud ectoderm cannot occur because components of the Hh signaling pathway and Hh target genes have not been found in this tissue. However, recent array-based data identified both the components necessary to activate the Hh signaling pathway and targets of this pathway in the limb bud ectoderm. Using immunohistochemistry and various methods of detection for targets of Hh signaling, we found that SHH protein and targets of Hh signaling are present in the limb bud ectoderm including the apex of the bud. To directly test whether ectodermal Hh signaling was required for normal limb patterning, we removed\n                    <jats:italic>Smo<\/jats:italic>\n                    , an essential component of the Hh signaling pathway, from the apical ectodermal ridge (AER). Loss of functional Hh signaling in the AER resulted in disruption of the normal digit pattern and formation of additional postaxial cartilaginous condensations. These data indicate that contrary to previous accounts, the Hh signaling pathway is present and required in the developing limb AER for normal autopod development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0912818107","type":"journal-article","created":{"date-parts":[[2010,3,9]],"date-time":"2010-03-09T00:29:02Z","timestamp":1268094542000},"page":"5489-5494","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":44,"title":["Shh pathway activation is present and required within the vertebrate limb bud apical ectodermal ridge for normal autopod patterning"],"prefix":"10.1073","volume":"107","author":[{"given":"Cortney M.","family":"Bouldin","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, The Genetics Institute, University of Florida, Gainesville, FL 32610;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Gritli-Linde","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 12F, SE-41390, G\u00f6teborg, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohyun","family":"Ahn","sequence":"additional","affiliation":[{"name":"Program in Genomics of Differentiation, Eunice Kennedy Shriver-National Institure of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Harfe","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, The Genetics Institute, University of Florida, Gainesville, FL 32610;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,3,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.21.4393"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.023"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.024"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06718"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2008.01.008"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.22.4811"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10056"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.10992"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80018-9"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1622"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.001966"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1693008"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90030-2"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90297-X"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1178"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02529"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168755"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096966"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07085"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.02.005"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.02.008"},{"key":"e_1_3_3_22_2","first-page":"877","article-title":"Interplay between the molecular signals that control vertebrate limb development","volume":"46","author":"Niswander L","year":"2002","unstructured":"L Niswander, Interplay between the molecular signals that control vertebrate limb development. 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