1995 Fiscal Year Annual Research Report

筋細胞系譜の決定と分化の分子機構

Research Project

Project/Area Number	06304053
Research Institution	National Institute of Neuroscience, NCNP
Principal Investigator	鍋島陽一国立精神・神経センター, 神経研究所・遺伝子工学, 次長 (60108024)
Co-Investigator(Kenkyū-buntansha)	遠藤剛千葉大学, 理学部, 助教授 (30194038) 野地澄晴徳島大学, 工学部, 教授 (40156211) 真壁和裕京都大学, 大学院・理学研究科, 助手 (60222288) 大日方昴千葉大学, 理学部, 教授 (40012413) 浅島誠東京大学, 教養学部, 教授 (00090564)
Keywords	筋発生 / MyoDファミリー / 中胚葉誘導 / 筋収縮構造 / アクチン結合タンパク / 増殖因子 / bFGF / ソニックヘッジホック
Research Abstract	筋細胞系譜の決定と分化に関する研究を行い、次の結果を得た。 1.ツメガエルの胞胚のアニマルキャップにアクチビンを作用させることにより筋肉が分化するシステムを用いて筋細胞誘導にともなって発現する遺伝子カスケードを解析し、さらにmyf-5の発現を制御する因子の解析を行った。 2.筋細胞誘導に関与する増殖因子の候補としてFGF, Shh, BMP, HGF, Wn'tを解析した。FGFを側板中胚葉に強制発現させると肢芽さらにほぼ完全な肢を誘導すること、ShhがBMP2,BMP7,Wh't5aの発現誘導に寄与していることを明らかにした。 3.Myogeninが1次筋管細胞の形成のみならず、2次筋管細胞の形成も制御していることを明らかにした。Myogenin-/-の筋芽細胞を樹立した。bFGF,LPAなど異なる性質をもつ増殖因子が異なる性質をもつ筋芽細胞をもたらすこと、その作用点はMyoDの発現抑制、MyoDの機能抑制、Myogeninの発現誘導プロセスの3点であること、LPA、血清からの増殖シグナルは細胞密度の上昇、すなわち、接触阻害による分化誘導シグナルを打ち消すことが出来ないことが明らかになった。 4.筋収縮構造形成に重要なアクチンの重合を制御する因子、コフィリン、プロフィリン、ADPの発生における発現と細胞分裂時の分裂溝にコフィリンが濃縮すること、コフィリンのリン酸化が機能に重要えあることを明らかにした。また、骨格筋特異的なC蛋白を同定した。 5.筋管細胞で発現する低分子量G蛋白質を同定した。筋細胞の最終分化過程では一部の細胞がアポトーシスで死滅すること、この過程にフォスフォリパーゼCgが関与することを示した。 6.筋細胞系譜の決定を制御しているマイヨプラスミンの分子的実態を明らかにするためにサブトランクション法により、マイヨプラスミンで特異的に発現する遺伝子を分離した。

Research Products

(41 results)

All Other

All Publications (41 results)

[Publications] Hoshino M., Suzuki E., Nabeshima Y., and Hama C.: "Hikaru genki protein is secreted into clefts from an early stage of synapse formation in Drosophila." Development. (in press).
[Publications] Yoshida S., Fujisawa-Sehara A., Arai K. and Nabeshima Y.: "Lysophosphatidic acid and bFGF control different modes in proliferating myoblasts." J. Cell Biol.(in press).
[Publications] Yagami-Hiromasa T., Sato T., Kurisaki T.,Kamijo K., Nabeshiwa Y. and Fujisaki-Sehara A.: "A metalloprotease-disintegrin particingpata in myoblast fusion" Nature 377. 652-656 (1995)
[Publications] Hirata J., Nakagoshi H., Nabeshima Y. and Matsuzaki F.: "Asymmetric segregation of the homeodomain protein Prospero during Drosophila development." Nature 377. 627-630 (1995)
[Publications] Kuro-o M., Hanaoka K., Noguchi T., Hiroi Y., Fujimori Y., Takewaki S., Hayasaka M., Aikawa M., Katoh H., Miyagishi A., Nagai R., Yazaki Y., and Nabeshima Y.: "Overezpression of sodium-proton exchanger causes salt-sensitive blood pressure elevation in transgenic mice" Circulation Res.76. 148-153 (1995)
[Publications] Nakano, H., Uchiyama, H., Fukui, A., Sugino, H., Asashima, M.: "Inhibin/Activin βA-subunit monomer has Xenopus mesoderm-inducing activity" Hormone Resesrch. S2-991. 1-9 (1995)
[Publications] Koike, H., Nakamura, K., Nishimura, K., Kashima, I., Wiederhold, M.L., Asashima, M.: "Non-invasive assessment of otolith formation during development of the Japanses red-bellied newt, Cynops pyrrhogaster" Hearing Resech. 88. 206-214 (1995)
[Publications] Ariizumi, T., Asachima, M.: "Head and trunk-tail organizing effects of the gastrula ectoderm of Cynops pyrrhogaster after treatment with activin A." Roux Archives Develop. Biol.,. 2041. 427-435 (1995)
[Publications] Kinoshita, K., Bessho, T., Asashima, M.,: "Onset of the competence to respond to activin A in isolated eight-cell stage Xenopus animal blastomers." Develop. Growth Differ. 37. 303-309 (1995)
[Publications] Yokota, C., Mukasa, T., Higashi, M., Odaka, A., Marota, K., Uchiyama, H., Eto, Y., Asashima, M. and Momoi, T: "Activin Induces the Expression of the Xenopus Homologue of Sonic Hedgehog during Mesoderm Formation in Xenopus Explants" Biochem. Biophys. Res. Commun.,. 207(1). 1-7 (1995)
[Publications] M. L. Wiederhold, M. Yamashita, K. A. Larsen, J. S. Batten, H. Koike, M. Asashima: "Development of the otolith and semicircular canalsin the Japanese red-bellied newt, Cynops pyrrhogaster" Hearing Research. 84. 41-51 (1995)
[Publications] K. Sekiguchi, C. Yokota, T. Kaname, Q. -Wen-Fan, K. Kadomatsu, M. Asashima, T. Muramatsu: "Restricted expression of Xenopus midkine gene during early development." J. Biochemistry.118. 94-100 (1995)
[Publications] T. Yamagishi, S-I. Nishimatsu, S. Nomura, M. Asasgima, K. Murakami and N. Ueno: "Expression of BMP-2,4 genes during Xenopus early development." Zool. Science.12. 353-358 (1995)
[Publications] C. J. Pfeiffer, M. Asashima, M.Yamashita: "Ultrastructural cytology of the primitive lung of the newt, Cynops pyrrhogaster" J. Submic. Cytol. Path.27. 491-500 (1995)
[Publications] C. J. Pfeiffer, M. Yamashita, A.Izumi-Kurokawa, H. Koike, and M. Asashima: "Cytopathologic observation of the lung of adult newts (Cynops pyrrhogater) on-board the space shuttle, Columbia, during the second international microgravity labolatory experiments." J. Submic. Cytol. Path.27. 501-509 (1995)
[Publications] Y. Mogami, M. Imamizo, M. Yamasita, A. Izumi-Kurotani, M. L. Wiederhold, H. Koike, M. Asashima: "Astronewt : Early development of newt in space." Adv. Space Res.17. 257-263 (1995)
[Publications] S. Hatada, M. Kinoshita, M. Noda, M. Asashima: "Indentification of a Xenopus glutamine synthetase gene abundantly expressed in the embryunic nervous system but not in adult brain" FEBS Letters. 371. 287-292 (1995)
[Publications] T. Ariizumi, M. Asashima: "Control of the embryonic body plan by activin during amphibian development." Zool. Science. 12. 509-521 (1995)
[Publications] C. J. Pfeiffer, M. Asashima: "Ultrastructure of Rhabdias tokyoensis, the Parasitic Nematode of the Japanese Newt Lung." Diseases of Aquatic Organisms. (in press).
[Publications] K. Kinoshita, M. Asashima: "Effect of activin and lithium on isolated Xenopus animal blastomeres and response alteration at the midblastula transition." Development. 121. 1581-1589 (1995)
[Publications] Uchiyama, H., Komazaki, S., Asashima, M., and Kikuyama, S.: "Occurrance of immunoreactive actisin B in gonadtrophs, thyrotrophs, and somatotrophs of the Xenopus pituitary." Gen. Comp. Endocrinol.(in press).
[Publications] Ariizumi, T., Komazaki, S., Asashima, M., and G. M. Malacinski: "Activin treated urodele ectoderm : A model experomental system for cardiogenesis." Int. J. Develop. Biol.(in press).
[Publications] H. Koike, K. Nakamura, K. NIshimura, I. Kashihima, M. L. Wiederhold, M. Asashima: "Non-invasive assessment of otolith formation during development of the Japanese red-bellied newt, Cynops pyrrhogaster." Hearing Research. 88. 206-214 (1995)
[Publications] Nakano, H., Uchiyama, H., Fukui,A., Sugino, H., Asashima, M.: "Comparison of Mesoderm-Inducing Activity with Monomeric and Dimeric Inhibin Alpha and Beta-A Subunits on Xenopus Ectoderm." Hormone Research. 44(suppl 2),. 15-22 (1995)
[Publications] F. Myokai, N. Washio, Y. Asahara, T. Yamaai. N. Tanda, T. Ishikawa, S. Aoki, H. Kurihara, Y. Yamamura, T. Saito, Y. Matsuo, T. Nakamura, S. Noji, and T. Nohno.: "Expression of the hepatocyte growth factor gene during chick limb development." Dev. Dyn.202. 80-90 (1995)
[Publications] T. Takebayashi, M. Iwamoto, A. Jikko, T. Matsumura, M. Enomoto-Iwamoto, F. Myokai, E. Koyama, T. Yamaai, K. Matsumoto, T. Nakamura, K. Kurisu, and S. Noji: "Hepatocyte growth factor/scatter factor modulates cell motility proliferation, and proteoglycan sysnthesis of chondrocytes." J. Cell Biol.129. 1411-1419 (1995)
[Publications] H. Ohuchi, T. Nakagawa, M. Yamauchi, T. Ohata, H. Yoshioka, T. Kuwana, T. Mima, T. Mikawa, T. Nohno, and S. Noji: "An additional limb can be induced from the flank of the chick embryo by FGF4." Biochem. Biophys. Res. Commun.209. 809-816 (1995)
[Publications] T. Mima, H. Ohuchi, S. Noji, and T. Mikawa: "FGF can induce outgrowth of somatic mesoderm both inside and outside of limb-forming regions" Dev. Biol.,. 167. 617-620 (1995)
[Publications] T. Nohno, T. Ishikawa, K. Hosokawa, T. Saito, S. Noji, B. B. Koenig, S. R. Klise, D. H. Wolsing, J. S. Rosenbaum.: "Identification of a Human type II receptor for Bone Morphogenetic Proein-2 and -4 that forms heteromeric complex with type I receptor." J. Biol. Chem.,. 270. 22522-22526 (1995)
[Publications] T. Ishikawa, H. Yoshioka, H. Ohuchi, S. Noji, T. Nohno.: "Truncated type II receptor for BMP-4 induces secondary axial structures in Xenopus embryos" Biochem. Biophys. Res. Commun.,. 216. 26-33 (1995)
[Publications] Ono, S., Minami, N., Abe, H., and Obinata T.: "Characterization of a Novel Cofilin Isoform That Is Predominantly Expressed in Mammalian Skeletal Muscle." J. Biol. Chem.269. 15280-15286 (1995)
[Publications] Ohtsuka, Y., Nakae, H., Abe, H.,and Obinata, T.: "Immunochemical Studies of an Actin-Binding Protein in Ascidian Body Wall Smooth Muscle." Zool. Sci.11. 407-412 (1994)
[Publications] Koshida, S., Kurasawa, M., Yasuda, M., Sato, N., and Obinata, T.: "Assembly of Cardiac C-protein during Myofibrillogenesis in Myogenic Cells in Culture." Cell Struct. Func.20. 253-261 (1995)
[Publications] Yasuda, M., Koshida, S., Sato, N., and Obinata, T.: "Complete Primary Structure of Chicken Cardiac C-Protein (MyBP-C) and Its Expression in Developing Striated Muscles." J. Mol. Cell. Cardiol.27. 2275-2286 (1995)
[Publications] Nagaoka, R. Kusano, K., Abe, H., and Obinata, T.: "Effects of cofilin on actin filamentous structures in cultured muscle cells. Intracellular regulation of cofilin action." J. Cell Sci.108. 581-593 (1995)
[Publications] Nagaoka, R., Abe, H. Kusano, K., and Obinata, T.: "Concentration of cofilin, an small actin-binding protein, at the cleavage furrow during cytokinesis." Cell Motil. Cytoskeleton. 30. 1-7 (1995)
[Publications] Abe, H., Obinata, T., Minamide, L. S., and Bamburg, J. R.: "Xenopus laevis ADF/cofilin : a Phosphorylation-Regulated Protein Essential for Development." J. Cell Biol.(in press).
[Publications] Ohkubo, Y., Kishimoto, T., Nakata, T., Yasuda, H., & Endo, T.: "SV40 large T antigen reinduces the cell cycle in terminally differentiated myotubes through inducing Cdk2, Cdc2, and their partner cyclins." Exp. Cell Res.214. 270-278 (1995)
[Publications] Sakurai, T., Abe, Y., Kasuya, Y., Takuwa, N., Shiba, R., Yamashita, T., Endo, T., & Goto K.: "Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts without activation of mitogen-activated protein kinases." J. Biol. Chem.269. 14118-14122 (1995)
[Publications] Fukami, K., Sawada, N., Endo, T., & Takenawa, T.: "Identification of a phosphatidylinositol4,5-bisphosphate-binding site in chicken skeletal muscle a-actinin." J. Biol. Chem.271. 2646-2650 (1995)
[Publications] Yajima, H., Ohtsuka, H., Kume, H., Endo, T., Maruyama, K., Kimura, S., & Maruyama, K.: "Molecular cloning of a partial cDNA clone encoding the C terminal region of chicken breast muscle connectin." Zool. Sci.13. 119-123 (1996)

1995 Fiscal Year Annual Research Report

筋細胞系譜の決定と分化の分子機構

Principal Investigator

鍋島 陽一 国立精神・神経センター, 神経研究所・遺伝子工学, 次長 (60108024)

Research Products

[Publications] Hoshino M., Suzuki E., Nabeshima Y., and Hama C.: "Hikaru genki protein is secreted into clefts from an early stage of synapse formation in Drosophila." Development. (in press).

[Publications] Yoshida S., Fujisawa-Sehara A., Arai K. and Nabeshima Y.: "Lysophosphatidic acid and bFGF control different modes in proliferating myoblasts." J. Cell Biol.(in press).

[Publications] Yagami-Hiromasa T., Sato T., Kurisaki T.,Kamijo K., Nabeshiwa Y. and Fujisaki-Sehara A.: "A metalloprotease-disintegrin particingpata in myoblast fusion" Nature 377. 652-656 (1995)

[Publications] Hirata J., Nakagoshi H., Nabeshima Y. and Matsuzaki F.: "Asymmetric segregation of the homeodomain protein Prospero during Drosophila development." Nature 377. 627-630 (1995)

[Publications] Nakano, H., Uchiyama, H., Fukui, A., Sugino, H., Asashima, M.: "Inhibin/Activin βA-subunit monomer has Xenopus mesoderm-inducing activity" Hormone Resesrch. S2-991. 1-9 (1995)

[Publications] Koike, H., Nakamura, K., Nishimura, K., Kashima, I., Wiederhold, M.L., Asashima, M.: "Non-invasive assessment of otolith formation during development of the Japanses red-bellied newt, Cynops pyrrhogaster" Hearing Resech. 88. 206-214 (1995)

[Publications] Ariizumi, T., Asachima, M.: "Head and trunk-tail organizing effects of the gastrula ectoderm of Cynops pyrrhogaster after treatment with activin A." Roux Archives Develop. Biol.,. 2041. 427-435 (1995)

[Publications] Kinoshita, K., Bessho, T., Asashima, M.,: "Onset of the competence to respond to activin A in isolated eight-cell stage Xenopus animal blastomers." Develop. Growth Differ. 37. 303-309 (1995)

[Publications] Yokota, C., Mukasa, T., Higashi, M., Odaka, A., Marota, K., Uchiyama, H., Eto, Y., Asashima, M. and Momoi, T: "Activin Induces the Expression of the Xenopus Homologue of Sonic Hedgehog during Mesoderm Formation in Xenopus Explants" Biochem. Biophys. Res. Commun.,. 207(1). 1-7 (1995)

[Publications] M. L. Wiederhold, M. Yamashita, K. A. Larsen, J. S. Batten, H. Koike, M. Asashima: "Development of the otolith and semicircular canalsin the Japanese red-bellied newt, Cynops pyrrhogaster" Hearing Research. 84. 41-51 (1995)

[Publications] K. Sekiguchi, C. Yokota, T. Kaname, Q. -Wen-Fan, K. Kadomatsu, M. Asashima, T. Muramatsu: "Restricted expression of Xenopus midkine gene during early development." J. Biochemistry.118. 94-100 (1995)

[Publications] T. Yamagishi, S-I. Nishimatsu, S. Nomura, M. Asasgima, K. Murakami and N. Ueno: "Expression of BMP-2,4 genes during Xenopus early development." Zool. Science.12. 353-358 (1995)

[Publications] C. J. Pfeiffer, M. Asashima, M.Yamashita: "Ultrastructural cytology of the primitive lung of the newt, Cynops pyrrhogaster" J. Submic. Cytol. Path.27. 491-500 (1995)

[Publications] Y. Mogami, M. Imamizo, M. Yamasita, A. Izumi-Kurotani, M. L. Wiederhold, H. Koike, M. Asashima: "Astronewt : Early development of newt in space." Adv. Space Res.17. 257-263 (1995)

[Publications] S. Hatada, M. Kinoshita, M. Noda, M. Asashima: "Indentification of a Xenopus glutamine synthetase gene abundantly expressed in the embryunic nervous system but not in adult brain" FEBS Letters. 371. 287-292 (1995)

[Publications] T. Ariizumi, M. Asashima: "Control of the embryonic body plan by activin during amphibian development." Zool. Science. 12. 509-521 (1995)

[Publications] C. J. Pfeiffer, M. Asashima: "Ultrastructure of Rhabdias tokyoensis, the Parasitic Nematode of the Japanese Newt Lung." Diseases of Aquatic Organisms. (in press).

[Publications] K. Kinoshita, M. Asashima: "Effect of activin and lithium on isolated Xenopus animal blastomeres and response alteration at the midblastula transition." Development. 121. 1581-1589 (1995)

[Publications] Uchiyama, H., Komazaki, S., Asashima, M., and Kikuyama, S.: "Occurrance of immunoreactive actisin B in gonadtrophs, thyrotrophs, and somatotrophs of the Xenopus pituitary." Gen. Comp. Endocrinol.(in press).

[Publications] Ariizumi, T., Komazaki, S., Asashima, M., and G. M. Malacinski: "Activin treated urodele ectoderm : A model experomental system for cardiogenesis." Int. J. Develop. Biol.(in press).

[Publications] H. Koike, K. Nakamura, K. NIshimura, I. Kashihima, M. L. Wiederhold, M. Asashima: "Non-invasive assessment of otolith formation during development of the Japanese red-bellied newt, Cynops pyrrhogaster." Hearing Research. 88. 206-214 (1995)

[Publications] Nakano, H., Uchiyama, H., Fukui,A., Sugino, H., Asashima, M.: "Comparison of Mesoderm-Inducing Activity with Monomeric and Dimeric Inhibin Alpha and Beta-A Subunits on Xenopus Ectoderm." Hormone Research. 44(suppl 2),. 15-22 (1995)

[Publications] F. Myokai, N. Washio, Y. Asahara, T. Yamaai. N. Tanda, T. Ishikawa, S. Aoki, H. Kurihara, Y. Yamamura, T. Saito, Y. Matsuo, T. Nakamura, S. Noji, and T. Nohno.: "Expression of the hepatocyte growth factor gene during chick limb development." Dev. Dyn.202. 80-90 (1995)

[Publications] H. Ohuchi, T. Nakagawa, M. Yamauchi, T. Ohata, H. Yoshioka, T. Kuwana, T. Mima, T. Mikawa, T. Nohno, and S. Noji: "An additional limb can be induced from the flank of the chick embryo by FGF4." Biochem. Biophys. Res. Commun.209. 809-816 (1995)

[Publications] T. Mima, H. Ohuchi, S. Noji, and T. Mikawa: "FGF can induce outgrowth of somatic mesoderm both inside and outside of limb-forming regions" Dev. Biol.,. 167. 617-620 (1995)

[Publications] T. Ishikawa, H. Yoshioka, H. Ohuchi, S. Noji, T. Nohno.: "Truncated type II receptor for BMP-4 induces secondary axial structures in Xenopus embryos" Biochem. Biophys. Res. Commun.,. 216. 26-33 (1995)

[Publications] Ono, S., Minami, N., Abe, H., and Obinata T.: "Characterization of a Novel Cofilin Isoform That Is Predominantly Expressed in Mammalian Skeletal Muscle." J. Biol. Chem.269. 15280-15286 (1995)

[Publications] Ohtsuka, Y., Nakae, H., Abe, H.,and Obinata, T.: "Immunochemical Studies of an Actin-Binding Protein in Ascidian Body Wall Smooth Muscle." Zool. Sci.11. 407-412 (1994)

[Publications] Koshida, S., Kurasawa, M., Yasuda, M., Sato, N., and Obinata, T.: "Assembly of Cardiac C-protein during Myofibrillogenesis in Myogenic Cells in Culture." Cell Struct. Func.20. 253-261 (1995)

[Publications] Yasuda, M., Koshida, S., Sato, N., and Obinata, T.: "Complete Primary Structure of Chicken Cardiac C-Protein (MyBP-C) and Its Expression in Developing Striated Muscles." J. Mol. Cell. Cardiol.27. 2275-2286 (1995)

[Publications] Nagaoka, R. Kusano, K., Abe, H., and Obinata, T.: "Effects of cofilin on actin filamentous structures in cultured muscle cells. Intracellular regulation of cofilin action." J. Cell Sci.108. 581-593 (1995)

[Publications] Nagaoka, R., Abe, H. Kusano, K., and Obinata, T.: "Concentration of cofilin, an small actin-binding protein, at the cleavage furrow during cytokinesis." Cell Motil. Cytoskeleton. 30. 1-7 (1995)

[Publications] Abe, H., Obinata, T., Minamide, L. S., and Bamburg, J. R.: "Xenopus laevis ADF/cofilin : a Phosphorylation-Regulated Protein Essential for Development." J. Cell Biol.(in press).

[Publications] Ohkubo, Y., Kishimoto, T., Nakata, T., Yasuda, H., & Endo, T.: "SV40 large T antigen reinduces the cell cycle in terminally differentiated myotubes through inducing Cdk2, Cdc2, and their partner cyclins." Exp. Cell Res.214. 270-278 (1995)

[Publications] Sakurai, T., Abe, Y., Kasuya, Y., Takuwa, N., Shiba, R., Yamashita, T., Endo, T., & Goto K.: "Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts without activation of mitogen-activated protein kinases." J. Biol. Chem.269. 14118-14122 (1995)

[Publications] Fukami, K., Sawada, N., Endo, T., & Takenawa, T.: "Identification of a phosphatidylinositol4,5-bisphosphate-binding site in chicken skeletal muscle a-actinin." J. Biol. Chem.271. 2646-2650 (1995)

[Publications] Yajima, H., Ohtsuka, H., Kume, H., Endo, T., Maruyama, K., Kimura, S., & Maruyama, K.: "Molecular cloning of a partial cDNA clone encoding the C terminal region of chicken breast muscle connectin." Zool. Sci.13. 119-123 (1996)

鍋島陽一国立精神・神経センター, 神経研究所・遺伝子工学, 次長 (60108024)