{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:40:57Z","timestamp":1790865657768,"version":"4.1.0"},"reference-count":63,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2000,4,1]],"date-time":"2000-04-01T00:00:00Z","timestamp":954547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Critical Reviews in Oral Biology &amp; Medicine"],"published-print":{"date-parts":[[2000,4]]},"abstract":"<jats:p> Several neurotransmitters, in particular serotonin (5-HT), have demonstrated multiple functions during early development and mid-gestational craniofacial morphogenesis. Early studies indicated that 5-HT is present in the oocyte, where it appears to function as a regulator of cell cleavage. Later, it has a significant role during gastrulation, during which there are significant areas of 5-HT uptake in the primitive streak. Subsequently, in association with neurulation, 5-HT uptake is seen in the floor plate of the developing neural tube. During neural crest formation and branchial arch formation, 5-HT has been demonstrated to facilitate cell migration and stimulate cell differentiation. During morphogenesis of the craniofacial structures, 5-HT stimulates dental development and may aid in cusp formation. All of the most commonly prescribed anti-depressant drugs inhibit serotonin uptake, yet they do not appear to cause major craniofacial malformations in vivo. Given the wide spectrum of effects that 5-HT has during development, it is difficult to understand why these anti-depressants are not major teratogens. Redundancy within the system may allow receptor and uptake pathways to function normally even with lower than normal levels of circulating serotonin. Serotonin-binding proteins, that are expressed in most craniofacial regions at critical times during craniofacial development, may have a buffering capacity that maintains adequate 5-HT tissue concentrations over a wide range of 5-HT serum concentrations. Dental development appears to be particularly sensitive to even small fluctuations in concentrations of 5-HT. Therefore, it may be that children of patients who have received selective serotonergic re-uptake inhibitors (such as Prozac and Zoloft) or the less selective tricyclic anti-depressant drugs (such as Elavil) would be at a higher risk for developmental dental defects such as anodontia and hypodontia. In this review, the evidence supporting a role for 5-HT during mammalian craniofacial development is discussed. A series of models is proposed that may explain how the craniofacial effects of 5-HT are mediated. <\/jats:p>","DOI":"10.1177\/10454411000110020601","type":"journal-article","created":{"date-parts":[[2009,1,9]],"date-time":"2009-01-09T00:40:32Z","timestamp":1231461632000},"page":"230-239","source":"Crossref","is-referenced-by-count":74,"title":["The Role of Serotonin and Neurotransmitters During Craniofacial Development"],"prefix":"10.1177","volume":"11","author":[{"given":"Julian R.D.","family":"Moiseiwitsch","sequence":"first","affiliation":[{"name":"Department of Endodontics, School of Dentistry, CB 7450, University of North Carolina, Chapel Hill, NC 27599-7450, USA,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2000,4,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199712)210:4<383::AID-AJA3>3.0.CO;2-C"},{"key":"atypb2","unstructured":"Agrez MV, Ames MM, Lieber MM, Tyce GM ( 1984). 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