{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:26:31Z","timestamp":1789547191241,"version":"build-2803163510"},"reference-count":36,"publisher":"The Company of Biologists","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:p>The aristaless-related homeobox genes Prx1 and Prx2 are required for correct skeletogenesis in many structures. Mice that lack both Prx1 and Prx2 functions display reduction or absence of skeletal elements in the skull, face, limbs and vertebral column. A striking phenotype is found in the lower jaw, which shows loss of midline structures, and the presence of a single, medially located incisor. We investigated development of the mandibular arch of Prx1\u2212\/\u2212Prx2\u2212\/\u2212 mutants to obtain insight into the molecular basis of the lower jaw abnormalities. We observed in mutant embryos a local decrease in proliferation of mandibular arch mesenchyme in a medial area. Interestingly, in the oral epithelium adjacent to this mesenchyme, sonic hedgehog (Shh) expression was strongly reduced, indicative of a function for Prx genes in indirect regulation of Shh. Wild-type embryos that were exposed to the hedgehog-pathway inhibitor, jervine, partially phenocopied the lower jaw defects of Prx1\u2212\/\u2212Prx2\u2212\/\u2212 mutants. In addition, this treatment led to loss of the mandibular incisors. We present a model that describes how loss of Shh expression in Prx1\u2212\/\u2212Prx2\u2212\/\u2212 mutants leads to abnormal morphogenesis of the mandibular arch.<\/jats:p>","DOI":"10.1242\/dev.128.15.2929","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T20:22:08Z","timestamp":1619209328000},"page":"2929-2938","source":"Crossref","is-referenced-by-count":79,"title":["<i>Prx1<\/i>and<i>Prx2<\/i>are upstream regulators of sonic hedgehog and control cell proliferation during mandibular arch morphogenesis"],"prefix":"10.1242","volume":"128","author":[{"given":"Derk","family":"ten Berge","sequence":"first","affiliation":[{"name":"Hubrecht Laboratorium, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Hubrecht Laboratorium, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Korving","sequence":"additional","affiliation":[{"name":"Hubrecht Laboratorium, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Reijnen","sequence":"additional","affiliation":[{"name":"Hubrecht Laboratorium, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estia J.","family":"van Raaij","sequence":"additional","affiliation":[{"name":"Hubrecht Laboratorium, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fons","family":"Verbeek","sequence":"additional","affiliation":[{"name":"Hubrecht Laboratorium, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Gaffield","sequence":"additional","affiliation":[{"name":"Western Regional Research Center, ARS, USDA, Albany, CA 94710, USA*Present address: Stanford University Medical Center, Beckman Center for Genetic and Molecular Medicine, 279 Campus Drive, Stanford, CA 94305-5323, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Meijlink","sequence":"additional","affiliation":[{"name":"Hubrecht Laboratorium, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042604553622400_BEE-AND-THOROGOOD-1980","doi-asserted-by":"crossref","unstructured":"Bee, J. and Thorogood, P. 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