Mechanisms of axis formation during early vertebrate embryogenesis

脊椎动物早期胚胎发生过程中轴形成的机制

• 批准号: 13680805
• 负责人: HIBI Masahiko
• 金额: $ 2.3万
• 依托单位: RIKEN (The Institute of Physical and Chemical Research)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680805/
• 关键词: axis formation; zebrafish; homeobox gene; transcriptional repressor; dorsal organizer; BMP; negative feedback; head formation; ゼブラフイツシュ; 形態形成; 神経領域化; 神経細胞; ノックアウトマウス

In amphibian and teleost embryogenesis, the program initiating axis formation begins soon after fertilization. In these species, the dorsal determinants are believed to be initially localized to the vegetal pole, and then transported to the dorsal side of the embryo. The molecular nature of the dorsal determinants has not been elucidated. It is known that these molecules activate the canonical Wnt pathway, leading to the nuclear accumulation of β-catenin on dorsal side, which further stimulates the expression of genes involved in the dorsal organizer induction. The zebrafish homeobox gene bozozok acts downstream of the Wnt signaling pathway and is required for organizer induction. Bozozok functions as a transcriptional repressor and inhibits dorsal expression of a novel bomeobox gene ved. Ved also functions as a transcriptional repressor that represses organizer genes. We further found that ved functions redundantly with vox and vent to restrict the organizer domain. In this study, we also isolated the gene responsible for zebrafish ventralized mutant ogon by a positional cloning strategy and found that the ogon locus encodes a zebrafish homologue of Sizzled. Ogon/Sizzled functions as a negative feedback regulator of BMP signaling. In addition, we generated mice deficient in fez and fez-like, which are expressed specifically in forebarin during early embryogenesis.

在两栖类和硬骨鱼胚胎发生中，受精后不久就启动轴形成的程序，据信背侧决定簇最初位于植物极，然后转移到胚胎的背侧。背侧决定簇尚未阐明，已知这些分子激活经典 Wnt 通路，导致 β-连环蛋白在背侧核积聚，从而进一步刺激。斑马鱼同源盒基因 bozozok 在 Wnt 信号通路下游发挥作用，是组织者诱导所需的，并且可抑制新型 bomeobox 基因 ved 的背部表达。我们进一步发现 ved 与 vox 和 vent 一起发挥冗余作用来限制组织者结构域。研究中，我们还通过定位克隆策略分离了负责斑马鱼腹侧突变 Ogon 的基因，并发现 Ogon 基因座编码 Ogon/Sizzled 的斑马鱼同源物，其功能是 BMP 信号传导的负反馈调节剂。 fez 和 fez-like 缺陷，它们在早期胚胎发生过程中在前巴蛋白中特异性表达。

项目成果

Levkowitz, G. Zeller, J., Sirotkin, H.I., French, D., Schilbach, S., Hashimoto, H., Hibi, M., Talbot, W.S., and Rosenthal, A.: "Zinc finger protein too few controls the development of monoaminergic neurons"Nature Neuroscience,. 6. 28-33 (2003)

Levkowitz, G. Zeller, J.、Sirotkin, H.I.、French, D.、Schilbach, S.、Hashimoto, H.、Hibi, M.、Talbot, W.S. 和 Rosenthal, A.：“锌指蛋白对照太少

Shimizu, T., Yamanaka, Y., Nojima, H., Yabe, T., Hibi, M., Hirano, T.: "A novel repressor-type homeobox gene, ved, is involved in dharma/bozozok-mediated dorsal organizer formation in zebrafish"Mechanisms of Development. 118. 125-138 (2002)

Shimizu, T.、Yamanaka, Y.、Nojima, H.、Yabe, T.、Hibi, M.、Hirano, T.：“一种新型阻遏型同源盒基因 ved，参与 dharma/bozozok 介导的背侧

Ryu, S-L., Fujii, R., Yamanaka, Y., Shimizu, T., Yabe, T., Hirata, T., Hibi, M., Hirano, T.: "Regulation of dharma/bozozok by the Wnt pathway"Developmental Biology. 231. 397-409 (2001)

Ryu, S-L.、Fujii, R.、Yamanaka, Y.、Shimizu, T.、Yabe, T.、Hirata, T.、Hib, M.、Hirano, T.：“Wnt 途径对 dharma/bozozok 的调节

Ryu, S-L., Fujii, R., Yamanaka, Y., Shimizu, T., Yabe, T., Hirata, T., Hibi, M., Hirano, T: "Regulation of dharma/bozozok by the Wnt pathway"Development Biology. 231. 397-409 (2001)

Ryu, S-L.、Fujii, R.、Yamanaka, Y.、Shimizu, T.、Yabe, T.、Hirata, T.、Hib, M.、Hirano, T：“Wnt 途径对 dharma/bozozok 的调节”

Ryu, S-L, et al.: "Regulation of dharma/bozozok by the Wnt signal"Developmental Biology. 231. 397-409 (2001)

Ryu, S-L 等人：“Wnt 信号对 dharma/bozozok 的调节”发育生物学。