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Cranial NCC are formed dorsally in the cranial neural tube and migrate ventrally to form craniofacial skeletal elements as well as other tissues. Multiple extracellular signaling pathways regulate the migration, survival, proliferation, and differentiation of NCC. <jats:styled-content>Results:<\/jats:styled-content> In this study, we demonstrate that <jats:italic>Shh<\/jats:italic> expression in the oral ectoderm and pharyngeal endoderm is essential for mandibular development. We show that a loss of <jats:italic>Shh<\/jats:italic> in these domains results in increased mesenchymal cell death in pharyngeal arch 1 (PA1) after NCC migration. This increased cell death can be rescued in utero by pharmacological inhibition of p53. Furthermore, we show that epithelial SHH is necessary for the early differentiation of mandibular cartilage condensations and, therefore, the subsequent development of Meckel's cartilage, around which the dentary bone forms. Nonetheless, a rescue of the cell death phenotype does not rescue the defect in cartilage condensation formation. <jats:styled-content>Conclusions:<\/jats:styled-content> Our results show that SHH produced by the PA1 epithelium is necessary for the survival of post\u2010migratory NCC, and suggests a key role in the subsequent differentiation of chondrocytes to form Meckel's cartilage. <jats:italic>Developmental Dynamics 244:564\u2013576, 2015<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.24256","type":"journal-article","created":{"date-parts":[[2015,1,27]],"date-time":"2015-01-27T18:30:41Z","timestamp":1422383441000},"page":"564-576","source":"Crossref","is-referenced-by-count":60,"title":["Sonic hedgehog from pharyngeal arch 1 epithelium is necessary for early mandibular arch cell survival and later cartilage condensation differentiation"],"prefix":"10.1002","volume":"244","author":[{"given":"Katherine Kretovich","family":"Billmyre","sequence":"first","affiliation":[{"name":"Department of Cell Biology Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Klingensmith","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712216105"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.05.028"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)80052-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.11.022"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199904)214:4<291::AID-AJA2>3.0.CO;2-E"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.056929"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.020123"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10156"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.454"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604751103"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.019125"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.2.461"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20833"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.8.1671"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/383407a0"},{"key":"e_1_2_6_17_1","first-page":"59","article-title":"Expression of N\u2010cadherin, N\u2010CAM, fibronectin and tenascin is stimulated by TGF\u2010beta1, beta2, beta3 and beta5 during the formation of precartilage condensations","volume":"43","author":"Chimal\u2010Monroy J","year":"1999","journal-title":"Int J Dev Biol"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.20007"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.4.1061"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.2.439"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(07)00562-3"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075703"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0070-2153(05)66003-6","article-title":"Tgf\u2010beta superfamily and mouse craniofacial development: interplay of morphogenetic proteins and receptor signaling controls normal formation of the face","author":"Dudas M","year":"2005","journal-title":"Curr Top Dev Biol"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.2.403"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.100107"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1219"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02824"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-203"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","unstructured":"GubelmannC GattikerA MassourasA HensK DavidF DecouttereF RougemontJ DeplanckeB.2011.GETPrime: a gene\u2010 or transcript\u2010specific primer database for quantitative real\u2010time PCR. 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