caa a22 4500 477095070 CHVBK 20180405111525.0 cr unu---uuuuu 170330e19961201xx s 000 0 eng 10.1007/s004290050026 doi (NATIONALLICENCE)springer-10.1007/s004290050026 Regulation of gene expression in cultured embryonic mouse mandibular mesenchyme by serotonin antagonists [Elektronische Daten] [Julian R. D. Moiseiwitsch, J. M. Lauder]  During murine embryogenesis, uptake sites for the neurotransmitter serotonin (5-HT) are transiently expressed in craniofacial epithelial structures. Based on malformations produced in cultured mouse embryos exposed to uptake inhibitors or receptor ligands, we have proposed that 5-HT acts as a dose-dependent morphogenetic signal during critical periods of craniofacial development. Several 5-HT receptor subtypes are co-distributed with tenascin and the calcium binding protein S-100β in developing craniofacial mesenchyme. Since these molecules are thought to be important for craniofacial development, their regulation by 5-HT could mediate some of its morphogenetic actions. Mandibular mesenchyme cells, from E12 mouse embryos (plug day=E1), grown in micromass cultures were used as an in vitro model to investigate whether 5-HT regulates expression of these molecules. Immunocytochemistry revealed expression of S-100β, tenascin, cartilage proteoglycan core protein (a component of the cartilage matrix) and a variety of 5-HT receptors in these cultures. To block the actions of 5-HT (from serum in the culture medium), cultures were exposed to one of these selective 5-HT receptor antagonists and effects on expression were investigated using quantitative immunobinding and in situ hybridization assays. These antagonists differentially regulated expression of cartilage core protein, S-100β and tenascin. Antagonism of 5-HT3 receptors by Zofran or 5-HT1A receptors by NAN-190 reduced the amount of core protein, whereas antagonism of 5-HT2A-C receptors by mianserin had no significant effect. All three antagonists stimulated levels of tenascin mRNA and protein. Expression of S-100β mRNA and protein was inhibited by Zofran and stimulated by mianserin, whereas NAN-190 had no significant effect. The differential effects of antagonists suggest that in vivo, 5-HT could: (1) promote expression of cartilage core protein by activation of 5-HT3 or 5-HT1A receptors, (2) inhibit production of tenascin by activation of multiple receptors, (3) promote or inhibit synthesis of S-100β by activation of 5-HT3 or 5-HT2 receptors, respectively. These actions may be important components of the morphogenetic functions of 5-HT during craniofacial development. Springer-Verlag Berlin Heidelberg, 1996 Key words 5-HT nationallicence Receptors nationallicence Neurotransmitters nationallicence Craniofacial development nationallicence S-100β nationallicence Tenascin nationallicence Cartilage proteoglycan core protein nationallicence Chondrogenesis nationallicence Moiseiwitsch Julian R. D. Department of Cell Biology and Anatomy, School of Medicine, CB 7090, University of North Carolina, Chapel Hill, NC 27599-7090, USA Tel.: (919) 966-5020; Fax: (919) 966-1856, US aut Lauder J. M. Department of Cell Biology and Anatomy, School of Medicine, CB 7090, University of North Carolina, Chapel Hill, NC 27599-7090, USA Tel.: (919) 966-5020; Fax: (919) 966-1856, US aut https://doi.org/10.1007/s004290050026 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004290050026 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Moiseiwitsch Julian R. D. Department of Cell Biology and Anatomy, School of Medicine, CB 7090, University of North Carolina, Chapel Hill, NC 27599-7090, USA Tel.: (919) 966-5020; Fax: (919) 966-1856, US aut NATIONALLICENCE 700 1- Lauder J. M. Department of Cell Biology and Anatomy, School of Medicine, CB 7090, University of North Carolina, Chapel Hill, NC 27599-7090, USA Tel.: (919) 966-5020; Fax: (919) 966-1856, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer