{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:19:06Z","timestamp":1791299946219,"version":"4.1.0"},"reference-count":62,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[1999,11,1]],"date-time":"1999-11-01T00:00:00Z","timestamp":941414400000},"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":[[1999,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>There is growing evidence that implicates a role for Sonic hedgehog (SHH) in morphogenesis of the craniofacial complex. Mutations in human and murine SHH cause midline patterning defects that are manifested in the head as holoprosencephaly and cyclopia. In addition, teratogens such as jervine, which inhibit the response of tissues to SHH, also produce cyclopia. Thus, the loss of SHH signaling during early stages of neural plate patterning has a profound influence of craniofacial morphogenesis. However, the severity of these defects precludes analyses of SHH function during later stages of craniofacial development. We have used an embryonic chick system to study the role of SHH during these later stages of craniofacial development. Using a combination of surgical and molecular experiments, we show here that SHH is essential for morphogenesis of the frontonasal and maxillary processes (FNP and MXPs), which give rise to the mid-and upper face. Transient loss of SHH signaling in the embryonic face inhibits growth of the primordia and results in defects analogous to hypotelorism and cleft lip\/palate, characteristics of the mild forms of holoprosencephaly. In contrast, excess SHH leads to a mediolateral widening of the FNP and a widening between the eyes, a condition known as hypertelorism. In severe cases, this widening is accompanied by facial duplications. Collectively, these experiments demonstrate that SHH has multiple and profound effects on the entire spectrum of craniofacial development, and perturbations in SHH signaling are likely to underlie a number of human craniofacial anomalies.<\/jats:p>","DOI":"10.1242\/dev.126.21.4873","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T03:53:41Z","timestamp":1619409221000},"page":"4873-4884","source":"Crossref","is-referenced-by-count":292,"title":["The role of Sonic hedgehog in normal and abnormal craniofacial morphogenesis"],"prefix":"10.1242","volume":"126","author":[{"given":"Diane","family":"Hu","sequence":"first","affiliation":[{"name":"University of California at San Francisco Department of Orthopaedic Surgery, School of Medicine, U-453 , , 533 Parnassus Avenue, San Francisco, CA 94143-0514, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Helms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,11,1]]},"reference":[{"key":"2023090607581879500_DEVELOP_126_21_4873C1","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1242\/dev.124.2.391","article-title":"Ectopic application of recombinant BMP-2 and BMP-4 can change patterning of developing chick facial primordia","volume":"124","author":"Barlow","year":"1997","journal-title":"Development"},{"key":"2023090607581879500_DEVELOP_126_21_4873C2","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/ng1196-353","article-title":"Identification of Sonic hedgehog as a candidate gene in holoprosencephaly","volume":"14","author":"Belloni","year":"1996","journal-title":"Nature Genetics"},{"key":"2023090607581879500_DEVELOP_126_21_4873C3","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/383407a0","article-title":"Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function","volume":"383","author":"Chiang","year":"1996","journal-title":"Nature"},{"key":"2023090607581879500_DEVELOP_126_21_4873C4","first-page":"196","article-title":"Perspectives on holoprosencephaly: Part II. 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