| Project/Area Number |
14580731
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
YAGINUMA Hiroyuki Fukushima Medical University, Department of Anatomy, Professor, 医学部, 教授 (90230193)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Noboru Fukushima Medical University, Department of Anatomy, Lecturer, 医学部, 講師 (00254756)
HOMMA Shunsaku Fukushima Medical University, Department of Anatomy, Lecturer, 医学部, 講師 (20261795)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | motoneuron / cervical cord / chick embryo / Lim3 / programmed cell death / LIM-HD / apoptosis / LIM転写因子 / レトロウイルスベクタ / 運動神経 / エレクトロポレーション / Bcl-2 |
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| Research Abstract |
In the avian embryo spinal cord, motoneurons (MNs) undergo programmed cell death (PCD) at two distinct periods. One is observed at relatively later stages (E6-E10, in the chick) and involves all segments of the spinal cord. By contrast, the other occurs at relatively earlier stages (E4-E5) and only in the non-limb innervating cervical spinal cord. To determine the identity of the dying MNs in the early type of cell death, we examined expression of subgroup-specific MN markers (Isl1, Isl2, Lim3 and MNR2) in the dying MNs of the chick embryo. Quantitative analysis revealed that PCD occurs only in a subgroup of MNs that express Isl1, Isl2 and MNR2 but do not express Lim3. MNs of this subgroup become postmitotic between E3 (-) and E3.5 and appear as a distinct subgroup in the dorsolateral region of the ventral horn by E4 after losing Lim3 expression. However, they disappear by E5. Following introducing Bcl-2 gene with retroviral vector, cervical MNs were rescued from cell death. After the period of cell death (E5), we observed that, in the infected embryos, there was an additional subgroup of MNs that expressed Isl1 and Isl2 but did not express Lim3. Similar MNs appear also in the thoracic region and develop into MNs that innervate intercostal muscles. These results suggest that this type of PCD of MN in the cervical spinal cord occurs only in the Lim3-negative subgroup of MNs that correspond to MNs innervating intercostal muscles. To further examine the relations between Lim3 expression and cell death, we infected one side of the spinal cord with the retrovirus vector carrying chick Lim3 cDNA using electroporation technique. On the infected side, the number of dying MNs markedly decreased at E4.5 and the number of healthy MNs increased after the period of cell death (E5.5). These results suggest that the downregulation of Lim3 is involved in mechanisms that determine cells to die in the early type of cell death in the cervical spinal cord.
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