• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Cell Migration and Layer/Nuclear Formation

開催日 2014/9/12
時間 16:00 - 17:00
会場 Room J(313+314)
Chairperson(s) 見学 美根子 / Mineko Kengaku (京都大学 物質-細胞統合システム拠点 / Instituete for Integrated Cell-Material Sciences(iCeMS), Kyoto University, Japan)
前田 信明 / Nobuaki Maeda (公益財団法人東京都医学総合研究所神経回路形成プロジェクト / Neural Network Project, Tokyo Metropolitan Institute of Medical Science, Japan)

Maternally-derived ambient taurine plays a pivotal role in radial migration in the embryonic mouse neocortex by tonically activating GABAA receptors

  • O2-J-4-3
  • 福田 敦夫 / Atsuo Fukuda:1 古川 智範 / Tomonori Furukawa:1 山田 順子 / Junko Yamada:2 秋田 天平 / Tenpei Akita:1 松島 芳隆 / Yoshitaka Matsushima:3 柳川 右千夫 / Yuchio Yanagawa:4 
  • 1:浜松医大・医・神経生理 / Dept. Neurophysiol., Hamamatsu Univ. Sch. Med., Shizuoka, Japan 2:弘前大院・脳研・脳神経生理 / Dept. Neurophysiol., Hirosaki Univ. Grad. Sch. Med., Aomori, Japan 3:浜松医大・医・化学 / Dept. Chem., Hamamatsu Univ. Sch. Med., Shizuoka, Japan 4:群馬大院・医・脳神経発達統御・遺伝発達行動 / Dept. Genet. Behav. Neurosci., Gunma Univ. Grad. Sch. Med., Gunma, Japan 

Numerous studies suggest that endogenous GABAA receptor (GABAAR) activation is involved in neocortical development including migration. Those studies used GABAAR blockers by assuming endogenous agonist is GABA. We performed in utero electroporation of mRFP gene to mice in which GABA synthesizing enzyme (GAD67) gene (Gad1) is replaced by GFP gene (GAD67GFP/GFP, GAD67GFP/+ and GAD67+/+). Thus we could label (mRFP) cortical plate cells born on E14.5 under different ambient GABA levels. There were no differences in migration or GABA response of labeled cells among genotypes. However, continuous blockade of GABAAR accelerated radial migration. This GABAAR blockade in GAD67GFP/GFP mice suggested an existence of alternative endogenous GABAAR agonists. Thus, we tested a role for taurine, which is derived from maternal blood, but abundant in the fetal brain. Taurine-evoked currents in labeled cells were mediated by GABAAR. Taurine uptake was blocked by the taurine transporter inhibitor GES, and release of taurine was blocked by the volume-sensitive anion channel blocker DCPIB, as studied with HPLC in acute neocortical slices. GES increased extracellular taurine concentration and induced an inward shift of Ihold, which was reversed by a GABAAR antagonist. In embryonic taurine deficient model by maternal i.p. injection of optical isomer of taurine precursor (D-cysteinesulfinic acid), GABAAR-mediated tonic currents decreased and radial migration was accelerated. As tonic currents were equivalent among genotypes of GAD67-GFP knock-in mice, taurine rather than GABA might be an endogenous agonist of embryonic tonic GABAAR conductance. Thus, taurine may have agonistic effects on tonic GABAAR, to work as a stop signal for radially migrating cortical plate cells.

Copyright © Neuroscience2014. All Right Reserved.