Molecular Mechanism of Neuronal Differentiation Regulated by Primary Cilium

• Project/Area Number: 26460271
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: University of Yamanashi
• Principal Investigator: TAKEDA Sen 山梨大学, 総合研究部, 教授 (20272429)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 繊毛 / 神経幹細胞 / 細胞移動 / 神経分化 / 一次繊毛 / 神経細胞 / 細胞骨格 / 繊毛症候群 / 細胞運動 / アクチン / GFP / カルシウム

Outline of Final Research Achievements

Neurons are the fundamental components of brain and are woven into the glial and vascular cytoarchitecture, whose internal space is filled with interstitial fluid forming microenvironment. Therefore, neurons may receive various signals from surrounding milieu to modulate their function. In this study, I focused on the molecular receptive mechanism, intracellular signaling relay and the behavior of neurons during development in terms of primary cilia installed on the neurons. This study revealed that melanin concentrating hormone (MCH) regulates the length of cilia via G-protein coupled receptors (GPCRs), whose downstream is mediated by cAMP. Moreover, it implies the importance of cilia in regulating the migration of neuronal stem cell towards pail surface via ciliary guidance. Collectively, this study provides several lines of evidence that primary cilia contribute to the neurogenesis. This will pave the way for elucidating the pathogenesis of neuronal ciliopathy.

Research Products

• [Journal Article] Modulation of primary cilia length by melanin-concentrating hormone receptor 1. Cell Signaling (2016)
  • Author(s): Hamamoto A, Yamato S, Katoh Y, Nakayama K, Yoshimura K, Takeda S, Kobayashi Y, *Saito Y
  • Journal Title: Cellular Signalling Volume: 28 Issue: 6 Pages: 272-584
  • DOI: 10.1016/j.cellsig.2016.02.018
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 9 + 0 and 9 + 2 cilia are randomly dispersed in the mouse node. (2016)
  • Author(s): Odate T, Takeda S, Narita K, Kawahara T.
  • Journal Title: Microscopy (Oxf) Volume: 65 Issue: 2 Pages: 119-126
  • DOI: 10.1093/jmicro/dfv352
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport (2015)
  • Author(s): Narita K, Sasamoto S, Koizumi S, Okazaki S, Nakamura H, Inoue T, Takeda S.
  • Journal Title: FASEB Journal Volume: 29 Issue: 6 Pages: 2247-59
  • DOI: 10.1096/fj.14-261396
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cilia in the choroid plexus: their roles in hydrocephalus and beyond (2015)
  • Author(s): Narita K, Takeda S.
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 9 Pages: 1-5
  • DOI: 10.3389/fncel.2015.00039
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Observation of the ciliary movement of choroid plexus epithelial cells ex vivo (2015)
  • Author(s): Inoue T, Narita K, Nonami Y, Nakamura H, Takeda S.
  • Journal Title: Journal of visual experiment Volume: 未定 Issue: 101 Pages: 572-584
  • DOI: 10.3791/52991
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Remarks] 研究室ホームページ
  • URL: http://www.cellbiology.jp