title: Differential patterning of genes involved in serotonin metabolism and transport in extra-embryonic tissues of the mouse.
abstract: Serotonin (5-HT) is an important neuromodulator, but recently has been shown to be involved in neurodevelopment. Although previous studies have demonstrated that the placenta is a major source of forebrain 5-HT during early forebrain development, the processes of how 5-HT production, metabolism, and transport from placenta to fetus are regulated are unknown. As an initial step in determining the mechanisms involved, we investigated the expression patterns of genes critical for 5-HT system function in mouse extraembryonic tissues.
  
  
  
  Mid-through late gestation expression of 5-HT system-related enzymes, Tph1, Ddc, Maoa, and 5-HT transporters, Sert/Slc6a4, Oct3/Slc22a3, Vmat2/Slc18a2, and 5-HT in placenta and yolk sac were examined, with cell type-specific resolution, using multiplex fluorescent in situ hybridization to co-localize transcripts and immunocytochemistry to co-localize the corresponding proteins and neurotransmitter.
  
  
  
  Tph1 and Ddc are found in the syncytiotrophoblast I (SynT-I) and sinusoidal trophoblast giant cells (S-TGC), whereas Maoa is expressed in SynT-I, syncytiotrophoblast II (SynT-II) and S-TGC. Oct3 expression is observed in the SynT-II only, while Vmat2 is mainly expressed in S-TGC. Surprisingly, there were comparatively high expression of Tph1, Ddc, and Maoa in the yolk sac visceral endoderm.
  
  
  
  In addition to trophoblast cells, visceral endoderm cells in the yolk sac may contribute to fetal 5-HT production. The findings raise the possibility of a more complex regulation of 5-HT access to the fetus through the differential roles of trophoblasts that surround maternal and fetal blood space and of yolk sac endoderm prior to normal degeneration.
authors.affiliation: Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Hsiao-Huei
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Sera
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Institute for the Developing Mind, The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: Plevitt@med.usc.edu.
authors.forename: Pat
authors.initials: P
authors.lastname: Levitt
mesh_terms: D000818:Animals; D005260:Female; D015870:Gene Expression; D051379:Mice; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000378:metabolism; D015017:Yolk Sac / Q000378:metabolism*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase
keywords: Placenta; Serotonin; Sinusoidal trophoblast giant cells; Syncytiotrophoblast; Yolk sac