1998 Fiscal Year Annual Research Report

脊椎動物頭部形態形成の遺伝発生学的解析

Research Project

Project/Area Number	08102009
Research Institution	Kumamoto University
Principal Investigator	相沢慎一熊本大学, 医学部, 教授 (60073011)
Co-Investigator(Kenkyū-buntansha)	村田卓也熊本大学, 医学部, 助手 (70305001) 松尾勲熊本大学, 医学部, 助教授 (10264285)
Keywords	Otx / Emx / 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 / シスエレメント / 終脳形成
Research Abstract	前年度に引き続き、Otx2が関わるヘッドオーガナイザー機能、原脳形成、Otx,Emxファミリーの遺伝子による原脳領域化の分子機序を明らかにする目的で、エンハンサー解析を中心に検討を進めた。 1) Deletion analysisによりOtx2遺伝子のヘッドオーガナイザーでの発現を規定するエンハンサーを約170bpに限局した。しかしこれ以上の限局は出来ず、ヒトOtx2の相当領域と配列を比較したところ、ほぼ完全に配列が一致していることが明らかとなった。すなわち、この領域の重要性は明らかとなったがコア-エレメントの推定には至らなかった。現在フグ及びニワトリで相同領域の同定を進めており、配列の比較からコア-エレメントを推定して、mutation analysisによりこれを確定する計画である。 2) 上記170bpエンハンサーが活性を持つ領域として、ヘッドオーガナイザー機能を担うと考えられる胚体外内胚葉領域(AVE)を特定した。AVEは最初胚の最も遠位部に位置するが、原条形成に先立って将来の頭部に移動し、必ずその反対側で原条形成の起こること、また、Otx2欠損下ではこの移動が起こらないまま異常な原条形成が起こり、頭部が欠損するを明らかにした。現在Otx2欠損AVEの頭部誘起能を実験発生学的に解析している。 3) 上流150kbまでに前脳エンハンサーの存在することをBACベクターを用いて確認し、その解析を進めるとともに、中脳エンハンサーの存在領域の同定を進めた。 4) Otx2遺伝子の代わりにOtx1遺伝子をノックインしたマウスを作成し、Otx1はOtx2のヘッドオーガナイザー因子としての機能、脊索前中軸内中胚葉における機能、原脳の領域化における機能の何れをも代替し得るが、原脳形成における機能は代替し得ないことを明らかにした。 4) Emx2/Emx1ダブル変異マウスを解析し、両遺伝子は終脳背側部で大脳半球と天井板の境界決定、現皮質領域の形成の他、新皮質の発達に中心的役割を果たすが、新皮質の形成それ自体は、別のメカニズムによって起こることを明らかにした。また、Otx2,Emx2ダブル変異マウスの解析を進め、両遺伝子が前脳の形成に協働していることを明らかにした。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Kuratani,S.et al.: "Rostral trucation of a cyclostome,Lampetra japonica,induced by all-transretinoic acid defines the head/trunk interface of the vertebrate body." Dev.Dyn.211. 35-51 (1998)
[Publications] Araki,T.et al.: "Changes in c-Jun but not Bcl-2 family proteins in p53-dependent apoptosis of mouse cerebellar granule neurons induced by by DNA damaging agent bleomycin." Brain Research.794. 239-247 (1998)
[Publications] Kuratani,S. et al.: "Stereotyped axonal Bundle Formation and Neruromeric Patterns in Embryos ob a Cyclostome,Lampetra japonica." J.Comparative Neurology. 391. 99-114 (1998)
[Publications] Yasui,K.et al.: "Expression of a twist-Related Gene,Bbtwist,during the Development of a Lancelet Species and Its Relation to Cephalochordate Anterior Structures." Dev.Biol.195. 49-59 (1998)
[Publications] Yin,Y.et al.: "Involvement of p85 in p53-dependent apoptotic response to oxidative stress." Nature. 391. 707-710 (1998)
[Publications] Ohta,M.et al.: "Suppression of Hematopoietic Activity in Tenascin-C-Deficient Mice." Blood. 91. 4047-4083 (1998)
[Publications] Kuratani,S.et s;.: "Rostral truncation of a cyclostome,Lampetra japonica,induced by all-transretinoic acid defines the head/trunk interface of the vertebrate body." Dev.Dyn.211. 35-51 (1998)
[Publications] Araji,T.et al.: "Changes in c-Jun but not Bcl-2 family proteins in p53-dependent apoptosis of mouse cerebellar granule neurons induced by DNA damaging agent bleomycin." Brain Research.794. 239-247 (1998)
[Publications] Kuratani,S.et al.: "Stereotyped Axonal Bundle Formation and Neruromeric Patterns in Embryos of a Cyclostome,Lampetra japonica." J.comparative Neurology. 391. 99-114 (1998)
[Publications] Yasui,K.et al.: "Expression of a twist-Related Gene,Bbtwist,during the Development of a Lancelet Species and Its Relation to Cephalochordate Anterior Structures." Dev.Biol.195. 49-59 (1998)
[Publications] Yin,Y.et al.: "Involvement of p85 in p53-dependent apoptotic response to oxidative stress," Nature. 391. 707-710 (1998)
[Publications] Ohta,M.et al.: "Suppression of Hematopoietic Activity in Tenascin-C-Deficient Mice." Blood. 91. 4047-4083 (1998)
[Publications] Minakawa,M.et al.: "Cerebellar cell lines established from a p53-deficient adult mouse." Brain Research. 813. 172-176 (1998)
[Publications] Suzuki,H.et al.: "Xid-Like Immunodeficiency in mice with Disruption of the p85a Subunit of Phosphoinositide 3-Kinase." Science. 283. 390-392 (1999)
[Publications] Suda,Y.et al.: "Functional equivalency between Otx2 and Otx1 in development of the rostral head." Development. 126. 743-757 (1999)
[Publications] Eto,K.et al.: "Role of NADH shuttle system in glucose-induced activation of mitochondorial metabolis] and insulin secretion." Science. 283. 981-985 (1999)
[Publications] Terauchi,Y.et al.: "Increased insulin sensitivity and hypoglycemia in mice lacking the p85a subunit of phoshphoinositide 3-kinase." Nature Genetics. 21. 230-235 (1999)
[Publications] Schmedt,C.et al.: "Csk controls antigen receptor-mediated development and selection of the lineage cells." Cell. (in press).

1998 Fiscal Year Annual Research Report

脊椎動物頭部形態形成の遺伝発生学的解析

Principal Investigator

相沢 慎一 熊本大学, 医学部, 教授 (60073011)

Research Products

[Publications] Kuratani,S.et al.: "Rostral trucation of a cyclostome,Lampetra japonica,induced by all-transretinoic acid defines the head/trunk interface of the vertebrate body." Dev.Dyn.211. 35-51 (1998)

[Publications] Araki,T.et al.: "Changes in c-Jun but not Bcl-2 family proteins in p53-dependent apoptosis of mouse cerebellar granule neurons induced by by DNA damaging agent bleomycin." Brain Research.794. 239-247 (1998)

[Publications] Kuratani,S. et al.: "Stereotyped axonal Bundle Formation and Neruromeric Patterns in Embryos ob a Cyclostome,Lampetra japonica." J.Comparative Neurology. 391. 99-114 (1998)

[Publications] Yasui,K.et al.: "Expression of a twist-Related Gene,Bbtwist,during the Development of a Lancelet Species and Its Relation to Cephalochordate Anterior Structures." Dev.Biol.195. 49-59 (1998)

[Publications] Yin,Y.et al.: "Involvement of p85 in p53-dependent apoptotic response to oxidative stress." Nature. 391. 707-710 (1998)

[Publications] Ohta,M.et al.: "Suppression of Hematopoietic Activity in Tenascin-C-Deficient Mice." Blood. 91. 4047-4083 (1998)

[Publications] Kuratani,S.et s;.: "Rostral truncation of a cyclostome,Lampetra japonica,induced by all-transretinoic acid defines the head/trunk interface of the vertebrate body." Dev.Dyn.211. 35-51 (1998)

[Publications] Araji,T.et al.: "Changes in c-Jun but not Bcl-2 family proteins in p53-dependent apoptosis of mouse cerebellar granule neurons induced by DNA damaging agent bleomycin." Brain Research.794. 239-247 (1998)

[Publications] Kuratani,S.et al.: "Stereotyped Axonal Bundle Formation and Neruromeric Patterns in Embryos of a Cyclostome,Lampetra japonica." J.comparative Neurology. 391. 99-114 (1998)

[Publications] Yasui,K.et al.: "Expression of a twist-Related Gene,Bbtwist,during the Development of a Lancelet Species and Its Relation to Cephalochordate Anterior Structures." Dev.Biol.195. 49-59 (1998)

[Publications] Yin,Y.et al.: "Involvement of p85 in p53-dependent apoptotic response to oxidative stress," Nature. 391. 707-710 (1998)

[Publications] Ohta,M.et al.: "Suppression of Hematopoietic Activity in Tenascin-C-Deficient Mice." Blood. 91. 4047-4083 (1998)

[Publications] Minakawa,M.et al.: "Cerebellar cell lines established from a p53-deficient adult mouse." Brain Research. 813. 172-176 (1998)

[Publications] Suzuki,H.et al.: "Xid-Like Immunodeficiency in mice with Disruption of the p85a Subunit of Phosphoinositide 3-Kinase." Science. 283. 390-392 (1999)

[Publications] Suda,Y.et al.: "Functional equivalency between Otx2 and Otx1 in development of the rostral head." Development. 126. 743-757 (1999)

[Publications] Eto,K.et al.: "Role of NADH shuttle system in glucose-induced activation of mitochondorial metabolis] and insulin secretion." Science. 283. 981-985 (1999)

[Publications] Terauchi,Y.et al.: "Increased insulin sensitivity and hypoglycemia in mice lacking the p85a subunit of phoshphoinositide 3-kinase." Nature Genetics. 21. 230-235 (1999)

[Publications] Schmedt,C.et al.: "Csk controls antigen receptor-mediated development and selection of the lineage cells." Cell. (in press).

相沢慎一熊本大学, 医学部, 教授 (60073011)