{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:44:31Z","timestamp":1792727071686,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,2,15]],"date-time":"2002-02-15T00:00:00Z","timestamp":1013731200000},"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":[[2002,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Development of the human craniofacial anatomy involves a number of interrelated, genetically controlled components. The complexity of the interactions between these components suggests that interference with the spaciotemporal interaction of the expanding tongue and elongating Meckel's cartilage correlates with the appearance of cleft palate. Mice homozygous for the semi\u2010dominant <jats:italic>Col2a1<\/jats:italic> mutation Disproportionate micromelia (<jats:italic>Dmm<\/jats:italic>), presenting at birth with both cleft palate and micrognathia, provide the opportunity to test the hypothesis that mandibular growth retardation coincides with formation of the secondary palate as predicted from our understanding of the Pierre Robin sequence. The present study was conducted in embryonic day 14 (E14) mice, 1 day before palate closure, to describe the relationship between growth of the lower jaw\/tongue complex versus genotype of the embryo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole heads, isolated from E14.25, E14.5 and E14.75 wild\u2010type and homozygous mutant embryos, were fixed in Bouin's solution, embedded in paraffin, and serially sectioned. Mid\u2010sagittal sections, stained with toluidine blue, were used to estimate growth of both tongue and lower jaw (Meckel's cartilage length) during a 12\u2010hr period preceding palate closure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In control embryos, the largest increase in Meckel's cartilage length occurred between E14.5 and E14.75. Compared to control, the mean Meckel's cartilage length in the mutant was similar at E14.25, but was significantly less at E14.5 and E14.75. Absolute tongue size in control embryos increased linearly during this period of E14.25 to E14.75. Relative to the rapidly growing Meckel's cartilage, however, relative tongue size in control embryos actually decreased over time. Absolute tongue size in the mutant was not significantly different from that of control at any of the embryonic stages examined, however, relative tongue size in the mutant was significantly greater at E14.75 compared to control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Mandibular growth retardation, coupled with relative macroglossia in E14 <jats:italic>Dmm<\/jats:italic>\/<jats:italic>Dmm<\/jats:italic> mice, suggests that the concerted development of the palate and lower jaw complex in the mutant is aberrant. Detection of micrognathia and pseudomacroglossia in homozygotes, before the time of palate closure, supports the hypothesis that a relationship exists between growth retardation of Meckel's cartilage and malformation of the secondary palate, as predicted by the Pierre\u2010Robin sequence. Teratology 65:116\u2013120, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/tera.10022","type":"journal-article","created":{"date-parts":[[2004,10,25]],"date-time":"2004-10-25T15:38:30Z","timestamp":1098718710000},"page":"116-120","source":"Crossref","is-referenced-by-count":41,"title":["Altered mandibular development precedes the time of palate closure in mice homozygous for disproportionate micromelia: An oral clefting model supporting the Pierre\u2010Robin sequence"],"prefix":"10.1002","volume":"65","author":[{"given":"James E.","family":"Ricks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria M.","family":"Ryder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura 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