マウス胚のオーガナイザー・脊索形成に関与する新規転写因子の単離と機能解析

• Project/Area Number: 11680722
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Osaka University
• Principal Investigator: SASAKI Hiroshi Osaka Univ., IMCB, Assistant professor, 細胞生体工学センター, 助手 (10211939)
• Project Period (FY): 1999 – 2000
• Project Status: Completed (Fiscal Year 2000)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: organizer / notochord / mouse / enhancer / transcriptional factor / Foxa2 / 遺伝子発現制御 / 原腸陥入 / Foxa2(HNF3β)

Research Abstract

Expression of a winged-helix transcription factor Foxa2/HNF3β is essential for development of the node and the notochord. We examined the node/notochord enhancer of mouse Foxa2 for sequence motifs conserved across vertebrate species. We cloned Foxa2 genes from chicken and fish, and identified respective node/notochord enhancers that were active in transgenic mouse embryos. Comparison of the sequences of the enhancers revealed three evolutionally conserved sequence motifs CS1, CS2 and CS3. Mutational analysis of the mouse enhancer indicated that CS3 is indispensable for gene expression in the node and the notochord, while CS1 and CS2 are required to augment enhancer activity. These motifs do not correspond to the consensus binding sequences of transcription factors known to be involved in node/notochord development.

Research Products

• [Publications] Nishizaki et al.: "Identification of essential sequence motifs in the node/notochord enhancer of Foxa2 (Hnf3β) gene that are conserved across vertebrate species."Mech.Dev.. (in press). (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Grachtchouk et al.: "Basal cell carcinomas in mice overexpressing Gli2 in skin."Nat.Genet.. 24. 216-217 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nishizaki, Y.Shimazu.K, Kondoh, H.and Sasaki, H.: "Identification of essential sequence motifs in the node/notochord enhancer of Foxa2 (Hnf3β) gene that are conserved across vertebrate species."Mech.Dev.. (in press). (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Grachtchouk, M., Mo, R., Yu, S., Zhang, X., Sasaki, H., Hui, C.C.and Dlugosz, A.A.: "Basal cell carcinomas in mice overexpressing Gli2 in skin."Nat.Genet.. 24. 216-217 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nishizaki et al.: "Identification of essential sequence motifs in the node/notochord enhancer of Foxa2 (Hnf3β) gene that are conserved across vertebrate species."Mech.Dev.. (In press). (2001)
• [Publications] Grachtchouk et al.: "Basal cell carcinomas in mice overexpressing Gli2 in skin."Nat.Genet.. 24. 216-217 (2000)
• [Publications] Sasaki H.: "Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling"Development. 126. 3915-3924 (1999)
• [Publications] Ding Q.: "Mouse Suppressor of fused is a negative regulator of Sonic hedgehog signaling and alters the subcellular distribution of Gli1"Curr. Biol.. 9. 1119-1122 (1999)