| Project/Area Number |
08102009
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kumamoto University |
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Principal Investigator |
SHINICHI Aizawa Kumamoto University Institute of Molecular Embryology and Genetics, Professor, 発生医学研究センター, 教授 (60073011)
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| Co-Investigator(Kenkyū-buntansha) |
AKIHITO Yamamoto Kumamoto University Institute of Molecular Embryology and Genetics, lecturer, 発生医学研究センター, 講師 (50244083)
ISAO Matsuo Kumamoto University Institute of Molecular Embryology and Genetics, Assintant, 発生医学研究センター, 助教授 (10264285)
村田 卓也 熊本大学, 医学部, 助手 (70305001)
植木 龍也 熊本大学, 医学部, 助手 (10274705)
倉谷 滋 熊本大学, 医学部, 助教授 (00178089)
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| Project Period (FY) |
1996 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥311,000,000 (Direct Cost: ¥311,000,000)
Fiscal Year 2000: ¥62,000,000 (Direct Cost: ¥62,000,000)
Fiscal Year 1999: ¥62,000,000 (Direct Cost: ¥62,000,000)
Fiscal Year 1998: ¥62,000,000 (Direct Cost: ¥62,000,000)
Fiscal Year 1997: ¥54,000,000 (Direct Cost: ¥54,000,000)
Fiscal Year 1996: ¥71,000,000 (Direct Cost: ¥71,000,000)
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| Keywords | Otx2 / Emx / A-pax / Head development / Antenior neuroectoderm / Midbrain / Forebrain / Corticogenesis / Cephalic neural crest cells / 原始内胚葉 / エピブラスト / 吻側原始内胚葉 / シスエレメント / 吻側神経外胚葉 / 原皮質 / 脳領域化 / ノックアウトマウス / 頭部形態形成 / ヘッドオーガナイザー / 原子内胚葉 / 脳の部域化 / 終脳形成 / 0tx / ヘッドオ-ガナイザー / ヤツメウナギ / 中脳神経堤細胞 / 0tx2 / 0tx1 / Emx2 / Emx1 / 中枢神経堤細胞 |
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| Research Abstract |
Major achievements are as follows : (1) In epiblast Otx2 and Cripto cooperate to induce a unique cell population in distal visceral endoderm (DVE), embryonic part of visceral endoderm and extraembryonic ectoderm ; these structures fail to develop in Otx2/Cripto double mutants.
(2) Otx2-positive DVE thus induced suppresses the expression of posterior genes such as Cripto in distal epiblast, thereby generating the A-P axis initially in a P-D orientation.
(3) Then Otx2-positive DVE moves to future anterior yielding a unique population of anterior visceral endoderm (AVE). Otx2 is essential to this movement of DVE cells.
(4) AVE suppresses the expression of posterior markers in adjacent epiblast, thereby shifting their expression to future primitive streak region. This axis rotation establishes the final A-P axis. In Otx2 mutants the embryos develop with A-P axis in P-D orientation and fail to develop anterior structures.
(5) With the primitive streak formation, Otx2 becomes expressed in defini
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tive anterior mesendoderm (AME). In contrust to permissive signals by AVE, AME sends instructive signals to induce anterior neuroectdoderm.
(6) Thus Otx2 is an essential component in DVE/AVE, head organizer, while Cripto constitutes a trunk organizer. The double mutants develop only r1/2, and we propose this region as the ground state in mammalian body plan.
(7)In anterior neuroectoderm thus induced Otx2 functions to maintain the ectoderm ; the anterior neuroectoderm is once induced but lost by the lack of this Otx2 function.
(8) Otx2 and Otx1 cooperate for development of mesencephalon.
(9) Emx2 and Otx2 cooperate for development of archipallium, ventral and dorsal thalamus, and anterior pretectum. For development of posterior pretectum the Emx2 expression must be turned off. Emx2 also cooperates with Emx1 for development of archipallium.
(10) Emx1 and Emx2 cooperates in generation of Cajal-Retzius cells and subplate neurons ; the double mutants fail to establish laminar structures in neocortex.
(11) Otx2 is essential for development of mesencephalic neural crest cells ; neurocranium, opthalamic branch of the trigeminal nerve, mesencephalic-trigeminal neurons and mandible are lost by the the lack of this Otx2 function. Less
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