{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:06:05Z","timestamp":1760706365584},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2001,7,11]],"date-time":"2001-07-11T00:00:00Z","timestamp":994809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[2001,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Normal development of the face, eyes, and brain requires the coordinated expression of many genes. One gene that has been implicated in the development of each of these structures encodes the secreted protein, Sonic hedgehog (Shh). During central nervous system development, <jats:italic>Shh<\/jats:italic> is required for ventral specification along the entire neural axis. To further explore the role of Shh in chick brain and craniofacial development, we overexpressed Shh in the developing rostral neural tube<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In order to determine if <jats:italic>Shh<\/jats:italic> is sufficient to ventralize the forebrain, we localized ectopically recombinant Shh protein to the rostral neural tube of chick embryos. The resulting embryos were evaluated morphologically and by assaying gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Disruption in normal gene expression patterns was observed with a reduction or loss in expression of genes normally expressed in the dorsal forebrain (<jats:italic>wnt\u20103a<\/jats:italic>, <jats:italic>wnt\u20104<\/jats:italic>, and <jats:italic>Pax\u20106<\/jats:italic>) and expansion of ventrally expressed genes dorsally (<jats:italic>HNF\u20103\u03b2<\/jats:italic>, <jats:italic>Ptc<\/jats:italic>). In addition to the genetic alterations observed in the neural tube, a craniofacial phenotype characterized by a reduction in many cranial neural crest\u2010derived structures was observed. The eyes of Shh\u2010treated embryos were also malformed. They were small with expansion of the retinal pigmented epithelium, enlarged optic stalks, and a reduction of neural retina.<\/jats:p><jats:p>Discussion: The ectopic localization of recombinant Shh protein in the rostral neural tube resulted in severe craniofacial anomalies and alterations of gene expression predicted by other studies. The system employed appears to be a model for studying the embryogenesis of malformations that involve the brain, eyes, and face. Teratology 64:107\u2013113, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/tera.1052","type":"journal-article","created":{"date-parts":[[2002,9,10]],"date-time":"2002-09-10T23:28:20Z","timestamp":1031700500000},"page":"107-113","source":"Crossref","is-referenced-by-count":22,"title":["Brain, eye, and face defects as a result of ectopic localization of Sonic hedgehog protein in the developing rostral neural tube"],"prefix":"10.1002","volume":"64","author":[{"given":"Ilya","family":"Nasrallah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Golden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,7,11]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)80052-4"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1242\/dev.121.6.1755","article-title":"Expression of zebrafish nk2.2 is influenced by sonic hedgehog\/vertebrate hedgehog\u20101 and demarcates a zone of neuronal differentiation in the embryonic forebrain","volume":"121","author":"Barth KA","year":"1995","journal-title":"Development"},{"key":"e_1_2_1_4_1","first-page":"283","volume-title":"Molecular zoology: advances, strategies, and protocols","author":"Burke A","year":"1996"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-51"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80334-7"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-47"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90627-3"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90536-7"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/12186"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2439"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1242\/dev.114.3.743","article-title":"Retinal fate and ganglion cell differentiation are potentiated by acidic FGF in an in vitro assay of early retinal development","volume":"114","author":"Guillemot F","year":"1992","journal-title":"Development"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1050880104"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1997.8589"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90062-4"},{"key":"e_1_2_1_17_1","first-page":"290","volume-title":"Molecular and cellular approaches to neural development","author":"Jessell T","year":"1997"},{"key":"e_1_2_1_18_1","volume-title":"Smith's recognizable patterns of human malformations","author":"Jones K","year":"1996"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.24.5079"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90628-4"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511897948"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.10.3267"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.4.1225"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7513443"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80074-4"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90626-2"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90514-2"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90397-6"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-357"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.11.1847"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.14.2709"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80682-0"}],"container-title":["Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Ftera.1052","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tera.1052","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T13:33:10Z","timestamp":1700400790000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tera.1052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,7,11]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2001,8]]}},"alternative-id":["10.1002\/tera.1052"],"URL":"https:\/\/doi.org\/10.1002\/tera.1052","archive":["Portico"],"relation":{},"ISSN":["0040-3709","1096-9926"],"issn-type":[{"value":"0040-3709","type":"print"},{"value":"1096-9926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,7,11]]}}}