Regulation by serotonin of tooth-germ morphogenesis and gene expression in mouse mandibular explant cultures.
Serotonin (5-HT) stimulates tooth-germ development in embryonic mouse mandibular explant cultures, but it is not clear whether this is due to a direct action on epithelial-mesenchymal interactions, or whether development was stimulated indirectly by serotonergic regulation of other morphoregulatory molecules. A calcium-binding protein, S-100beta, and the extracellular-matrix molecule, tenascin, two molecules thought to be important in craniofacial development, together with cartilage proteoglycan core protein, a marker for chondrogenesis, are modulated by serotonergic ligands in mandibular micromass cultures. Here, it was demonstrated that 5-HT stimulates expression of cartilage proteoglycan core protein, and inhibits expression of S-100beta and tenascin in mandibular explants. Further, ondansetron (Zofran), a 5-HT3 receptor antagonist, and NAN-190, a 5-HT1A antagonist, reversed the serotonergic stimulation of core protein and tooth germ development. In contrast serotonergic modulation of S-100beta and tenascin expression was not reversed by any of the 5-HT receptor antagonists tested, although the 5-HT uptake inhibitor, fluoxetine, did reverse the effect of 5-HT on S-100beta expression, as well as tooth-germ development. These results support previous work suggesting that 5-HT plays an important part in craniofacial development, especially in dentinogenesis and chondrogenesis. However, the possibility that tenascin or S-100beta mediate the effects of 5-HT on tooth-germ development is not supported. Rather, these results raise the possibility that 5-HT may exert effects directly on tooth-germ morphogenesis mediated by intracellular uptake of 5-HT and/or activation of 5-HT1A and 5-HT3 receptors.
Moiseiwitsch
J R
JR
Department of Endodontics, School of Dentistry, University of North Carolina, Chapel Hill 27599-7450, USA. julian@dentistry.unc.edu
Raymond
J R
JR
Tamir
H
H
Lauder
J M
JM
D053674:Aggrecans; D000818:Animals; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020219:Chondrogenesis / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D009414:Nerve Growth Factors; D009805:Odontogenesis / Q000187:drug effects*; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011985:Receptors, Serotonin / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D019063:Tenascin / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014083:Tooth Germ / Q000196:embryology*
C508320:Acan protein, mouse; D053674:Aggrecans; D002135:Calcium-Binding Proteins; D009414:Nerve Growth Factors; D011509:Proteoglycans; D011985:Receptors, Serotonin; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012702:Serotonin Antagonists; D019063:Tenascin; D012701:Serotonin