title: In vitro enhanced differentiation of neural networks in ES gut-like organ from mouse ES cells by a 5-HT4-receptor activation.
abstract: Using an embryoid body (EB) culture system, we developed a functional organ-like cluster, a "gut", from mouse embryonic stem (ES) cells (ES gut). Each ES gut exhibited various types of spontaneous movements. In these spontaneously contracting ES guts, dense distributions of interstitial cells of Cajal (ICC) (c-kit, a transmembrane receptor that has tyrosine kinase activity, positive cells; gut pacemaker cells) and smooth muscle cells were discernibly identified, but enteric neural networks were not identified. In the present study, we succeeded in forming dense enteric neural networks by a 5-HT(4)-receptor (SR4) agonist, mosapride citrate (1-10 μM) added only during EB formation. Addition of an SR4-antagonist, GR113808 (10 μM) abolished the SR4-agonist-induced formation of enteric neural networks. The SR4-agonist (1 μM) up-regulated the expression of mRNA of SR4 and the SR4-antagonist abolished this upregulation. 5-HT per se exerted similar effects to those of SR4-agonist, though less potent. These results suggest SR4-agonist differentiated enteric neural networks, mediated via activation of SR4 in the ES gut.
authors.affiliation: Department of Physiology II, Nara Medical University, School of Medicine, Kashihara, Nara 634-8521, Japan. mtakaki@naramed-u.ac.jp
authors.forename: Miyako
authors.initials: M
authors.lastname: Takaki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Misawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsuyoshi
authors.forename: Isao
authors.initials: I
authors.lastname: Kawahara
authors.forename: Kei
authors.initials: K
authors.lastname: Goto
authors.forename: Guo-Xing
authors.initials: GX
authors.lastname: Zhang
authors.forename: Koji
authors.initials: K
authors.lastname: Obata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000294:innervation*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D009415:Nerve Net / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism; D058828:Serotonin 5-HT4 Receptor Agonists / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D009025:Morpholines; D058828:Serotonin 5-HT4 Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C062720:mosapride