the functions of the Rest gene in neural crest cells

• Project/Area Number: 25870292
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Developmental biology; General anatomy (including histology/embryology)
• Research Institution: Gifu University
• Principal Investigator: AOKI Hitomi 岐阜大学, 医学(系)研究科(研究院), 講師 (10550361)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 神経堤細胞 / 転写調節因子 / 神経分化制御 / 遺伝子組み換え / コンディショナルノックアウトマウス / 神経分化抑制 / 遺伝子組換え / 発生 / 分化

Outline of Final Research Achievements

RE1-silencing transcription factor (REST) is a transcriptional repressor of neural genes. Rest null mice have embryonic lethality which prevents further investigations of the functions of the Rest gene in vivo . I studied neonatal but not embryonic lethality that was characterized by gastrointestinal tract dilation in the neural crest cell (NCC)-specific Rest conditional knockout (CKO) mice. While no histological abnormalities except the thinning of the digestive tract as a consequence of the gas accumulation were found in the digestive tract of the mutant mice, they do not have proper gastric retention after oral dye administration and the reduction of acetylcholinesterase (AChE) activity in NCC-derived myenteric plexus in the stomach was detected. High CO2 concentration in the dilated digestive tract of the Rest CKO mice indicates a failure of gut function by underdeveloped cholinergic transmission in the enteric nervous system.

Research Products

• [Journal Article] White spotting phenotype induced by targeted REST disruption during neural crest specification to a melanocyte cell lineage. (2015)
  • Author(s): Aoki H, Hara A, Kunisada T.
  • Journal Title: Genes Cells. Volume: 5 Issue: 5 Pages: 439-449
  • DOI: 10.1111/gtc.12235
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neonatal lethality of neural crest cell-specific Rest knockout mice is associated with gastrointestinal distension caused by aberrations of myenteric plexus. (2014)
  • Author(s): Aoki H, Hara A, Oomori Y, Shimizu Y, Yamada Y, Kunisada T.
  • Journal Title: Genes Cells. Volume: 19 Issue: 10 Pages: 723-742
  • DOI: 10.1111/gtc.12172
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The stemness of neural crest cells and their derivatives. (2014)
  • Author(s): Kunisada T, Tezulka K, Aoki H, Motohashi T
  • Journal Title: Birth Defects Res C Embryo Today. Volume: 102 Issue: 3 Pages: 251-261
  • DOI: 10.1002/bdrc.21079
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Gastrointestinal dissension of neural crest cell specific Rest transcription factor CKO mice caused by the aberration of Myenteric plexus (2014)
  • Author(s): Takahiro KUNISADA, YasuhiroYAMADA, AkiraHARA, Hitomi AOKI
  • Organizer: 47th Annual Meeting of JSDB
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2014-05-27 – 2014-05-30