Analysis of the mechanisms of cell death that involves a specific subgroup of motoneurons.

• Project/Area Number: 18500266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Fukushima Medical University
• Principal Investigator: YAGINUMA Hiroyuki Fukushima Medical University, School of Medicine, Professor (90230193)
• Co-Investigator(Kenkyū-buntansha): HOMMA Shunsaku Fukushima Medical University, School of Medicine, Associate professor (20261795) ; MASUDA Tomoyuki Fukushima Medical University, School of Medicine, Assistant professor (70372828) ; 佐藤 昇 福島県立医科大学, 医学部, 講師 (00254756)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: programmed cell death / LIM homeodomoain / transcription factor / cervical / motoneuron / Hox / development / avian / 運動神経細胞 / アポトーシス / 鳥類 / 哺乳類 / 頸髄 / レーザーダイセクション法 / 細胞死 / ニワトリ胚 / マウス胎仔 / BH3 only protein / Bcl2ファミリー

Research Abstract

To determine the identity of the dying motoneurons (MNs) undergoing programmed cell death (PCD) at relatively early stages (E4-E5 in the chick embryo) and only in the non-limb innervating cervical spinal cord, we examined expression of subgroup-specific MN markers (Isl1, Is12, Lim3, MNR2 and Foxpl) in the dying MNs. PCD occurs only in a subgroup of MNs that express Isl1, Isl2, MNR2 and FoxPl but that lack Lim3 expression. This Lim3-negative (Lim3) MN subgroup appears as a distinct subpopulation in the dorsolateral region of the ventral horn by E4 after losing Lim3 expression and they are no longer observed by E5. However, following the rescue of MNs by Bc12 overexpression, Lim3- persisted at least until E5-5.5. When Lim3 was overexpressed on one side of the spinal cord, the number of dying MNs was markedly decreased at E4.5 and the number of surviving healthy MNs was increased after the period of cell death (E5.5). These results suggest that the downregulation of Lim3 is involved in the specification of the cell death fate of early dying cervical MNs. Furthermore, the fact that Foxpl is expressed by dying MNs suggests that Hox proteins that are specific to the cervical segments may play a role in this type of cell death. In situ hybridizaiton for Hox genes revealed that Hoxc5, Hoxa3, Hoxa5 are expressed by cervical motoneurons and their rostro-caudal extents of expression cover the segments where early motoneuron death occurs. These Hox genes might be involved in the determination of motoneuron subgroups that under go cell death.

Research Products

• [Journal Article] Netrin-1 acts as a repulsive guidance cue for sensory axonal projections toward the spinal cord. (2008)
  • Author(s): Masuda,T
  • Journal Title: J Neurosci 28 Pages: 10380-10385
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Netrin-1 acts as a repulsive guidance cue for sensory axonal projections toward the spinal cord (2008)
  • Author(s): Masuda, T., Watanabe, K., Sakuma, C., Ikenaka, K., Ono, K., Yaginuma, H.
  • Journal Title: J Neurosci 28 Pages: 10380-10385
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Guidance cues from the embryonic dorsal spinal cord chemoattract dorsal root ganglion axons. (2007)
  • Author(s): Masuda,T
  • Journal Title: Neuroreport 18 Pages: 1645-1649
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Guidance cues from the embryonic dorsal spinal cord chemoattract dorsal root ganglion axons (2007)
  • Author(s): Masuda, T., Sakuma, C., Taniguchi, M., Kobayashi, K., Kobayashi, K., Shiga, T., Yaginuma, H.
  • Journal Title: Neuroreport 18 Pages: 1645-1649
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Guidance cues from the embryonic dorsal spinal cord chemoattract dorsal root ganglion axons. (2007)
  • Author(s): Masuda T, Sakuma C, Taniguchi M, Kobayashi K, Kobayashi K, Shiga T, Yaeinuma H.
  • Journal Title: Neuroreoprt 18. Pages: 1645-9
  • Peer Reviewed
• [Journal Article] Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo. (2006)
  • Author(s): Sato N, Sakuma C, Sato Y, Gould TW, Oppenheim RW, Yagunuma H.
  • Journal Title: Cell Death Differ. 13・3 Pages: 435-45
• [Journal Article] Early motoneuron death in the cervical cord of the avian embryo occurs to eliminate a specific subgroup of motoneurons that correspond to the motoneurons innervating intercostal muscles (2006)
  • Author(s): H.YAGINUMA, N.SATO, S.HOMMA, N.KOBAYASHI, T.SHIMADA, C.SAKUMA
  • Journal Title: Soci. Neurosci. Abstr.
• [Presentation] 「くび」の発生と神経細胞死 (2008)
  • Author(s): 八木沼洋行
  • Organizer: 第113回日本解剖学会総会・全国学術集会
  • Place of Presentation: 大分
  • Year and Date: 2008-03-30
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Development of the neck region and cell death of motoneruons (2008)
  • Author(s): Hiroyuki Yaginuma
  • Organizer: Annual Meeting, Japanese Association of Anatomists
  • Place of Presentation: Ohita, Japan
  • Year and Date: 2008-03-30
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 鳥類胚の頚髄で起こる早期神経細胞死によって、胸髄の肋間筋を支配するの肋間筋を支配する運動神経に相当する細胞群が取り除かれる (2007)
  • Author(s): 八木沼洋行, 他
  • Organizer: Neuro2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-05
• [Remarks]
  • URL: http://www.fmu.ac.jp/kenkyu/Profiles/7/0000657/profile.html