Top > Search Research paper > (In Japanese)体の左右非対称性におけるlefty遺伝子の役割

(In Japanese)体の左右非対称性におけるlefty遺伝子の役割

Research report code R013000256
Posted date Oct 1, 2003
  • (In Japanese)濱田 博司
  • (In Japanese)大阪大学細胞生体工学センター
Research organization
  • (In Japanese)大阪大学細胞生体工学センター
Report name (In Japanese)体の左右非対称性におけるlefty遺伝子の役割
Technology summary (In Japanese)胚の左側半分のみで発現する新規TGF superfamily 因子leftyを突破口として,左右の位置情報の伝達・確立機構を検討した。2つの類似したlefty遺伝子(lefty-1, lefty-2)は,ともに左側に非対称に発現するが,発現部位が異なっていた。左右の決定における役割を解析した結果,lefty-1が他の左右決定因子が正中線を趨えて拡散することを防ぐバリアーとして働くこと,体の左を決定する因子はNodalであること, Lefty2はNodalのantagonistとして働いていることがわかった。Nodal,Lefty蛋白質の作用機構を解析した結果, Leftyは競合的にNodalのシグナルをブロックすることが判った。非対称臓器の原基に発現する転写因子Pitx2の非対称な発現はNodalによって直接誘導されることが判った。遺伝子発現制御領域を解析した結果,lefty-2とnodalは左側特異的エンハンサーにより,lefty-1は右側特異的サイレンサーにより制御されることが判った。ヒトのlefty遺伝子を探索した結果,同一染色体に隣接するlefty-1, -2に相当する二つの機能的遺伝子を同定した。
Research field
  • Gene expression
  • Cell physiology in general
  • Cell division and proliferation
  • Development (=generation) and differentiation
Published papers related (In Japanese)(1)Meno, C., Saijoh, Y., Fujii, H., Ikeda, M., Yokoyama, Y., Yokoyama, M., Toyoda, Y. and Hamada, H. (1996). Left-right asymmetric expression of the TGFβ-family member lefty in developing mouse embryo. Nature 381: 151-155.
(2)Meno, C., Ito, Y., Saijoh, Y., Matsuda, Y., Tashiro, K. and Hamada, H. (1997). Two closely-related left-right asymmetrically-expressed genes, lefty-1 and lefty-2: Their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos. Genes Cells. 2: 513-524.
(3)Meno, C., Shimono, A., Saijoh, Y., Yashiro, K., Mochida, K., Ohishi, S., Noji, S., Kondoh, H. and Hamada, H. (1998). lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal. Cell. 94: 287-297.
(4)Yoshioka, H., Meno C., Koshiba, K., Sugihara, M., Itoh, H., Ishimaru, Y., Inoue, T., Ohuchi, H., Semina, E.V., Murray, J.C., Hamada, H. and Noji, S. (1998) Ptx2, a bicoid homeobox gene, is involved in a Lefty-signaling pathway in determination of left-right asymmetry. Cell. 94: 299-305.
(5)Mochizuki, T., Saijoh, Y., Tsuchiya, K., Shirayoshi, Y., Takai, S., Taya, C., Yonekawa, H., Yamada, K., Nihei, H., Nakatsuji, N., Overbeek, P., Hamada, H., Yokoyama, T. (1998). Cloning of inv, a gene that controls left-right asymmetry and kidney development. Nature 395: 177-181.
(6)Saijoh, Y., Adachi, H., Mochida, K., Ohishi, S., Hirao, A., and Hamada, H. (1999) Distincttranscriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2. Genes Dev. 13: 259-269.
(7)Adachi, H., Saijoh, Y., Mochida, K., Ohishi, S., Hashiguchi, H., Hirao, A., and Hamada, H. (1999) Determination of left-right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer. Genes Dev. 13: 1589-1600.
(8)Meno, C.,* Gritmann, K.,* Ohfuji, Y., Heckscher, E., Ohishi, S., Mochida, K., Shimono, A., Kondoh, H., Talbot, W., Robertson, E.J., Schier, A.F. and Hamada, H. (1999). Mouse Lefty2 and zebrafish Antivin are feedback inhibitors of Nodal signaling during vertebrate gastrulation. (*equally contributed) Mol. Cell 4: 287-298.
(9)Okada, Y., Nonaka, S., Tanaka, Y., Saijoh, Y., Hamada, H., and Hirokawa, N. (1999). Abnormal nodal flow precedes situs inversus in iv and inv mutant mice. Mol. Cell 4: 459-468.
(10)Saijoh, Y., Adachi, H., Sakuma, R., Yeo, C.-Y., Yashiro, K., Watanabe, M., Hashiguchi, H., Yashiro, K., Kawabata, M., Miyazono, K., Whitman, M. and Hamada, H. (2000). Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes a transcription factor FAST2. Mol. Cell 5: 35-47.
(11)Ishimaru, Y., Yoshioka, H., Tao, H., Thisse, B., Thisse, C., Wright, C.V.E., Hamada, H., Ohuchi, H., and Noji, S. (2000). Asymmetric expression of antivin/lefty1 in the early chick embryo. Mech. Dev. 90: 115-118.
(12)Yashiro, K., Saijoh, Y., Sakuma, R., Sakai, Y., Tomita, N., Matsuda, Y., Okada, S. Monden, M. and Hamada, H. (2000). Distinct transcriptional regulation and phylogenetic diversity of human LEFTY genes. Genes Cell. 5: 343-357.
(13)Osada, S., Saijoh, Y., Frisch, A., Yeo, C.-Y., Adachi, H., Watanabe, M., Whitman, M., Hamada, H., and Wright, C.V. (2000). Activin/Nodal responsiveness and asymmetric expression of Xenopus nodal-related gene converge on a FAST-regulated module in intron 1. Development. 127: 2503-2514.
(14)Shiratori, H., Sakuma, R., Watanabe, M., Hashiguchi, H., Mochida, K., Nishino, J., Sakai, Y., Saijoh, Y., Whitman, M. and Hamada, H. (2001). Two step regulation of asymmetric Pitx2 expression: Initiation by Nodal signaling and maintenance by Nkx2. Mol. Cell 7: 137-149.
(15)Yamamoto, M., Meno, C., Sakai, Y., Shiratori, H., Mochida, K., Ikawa, Y., Saijoh, Y., and Hamada, H. (2001) A transcription factor FoxH1/FAST mediates Nodal signaling during anterio-posterior patterning and node formation in the mouse. Genes & Dev. in press
Research project
  • Core Research for Evolutional Science and Technology;Genetic Programming
Information research report
  • (In Japanese)濱田 博司. 体の左右非対称性が生じる機構. 戦略的基礎研究推進事業 「生命活動のプログラム」 平成7年度 採択研究課題 終了シンポジウム 講演予稿集,2001. p.22 - 25.