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Molecular mechanisms of determination of limb region and identity

确定肢体区域和身份的分子机制

基本信息

批准号：
13480242
负责人：
TAMURA Koji
金额：
$ 11.01万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
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/en/grant/KAKENHI-PROJECT-13480242/
关键词：
Development Limb Limb bud Tbx Pattern formation Anterior-posterior axis Tereost Gene 胚芽形態形成鰭 identity 体節誘導前肢後肢遺伝子発現軟骨魚類

项目摘要

1.Mechanism of regionalization of splanchnic/somatic lateral plateOur explant studies showed that the lateral plate mesoderm, which eventually is separated into splanchnic/somatic layers, has already been regionalized along the anterior-posterior axis, and they suggested that the two layers specify their antero-posterior patttern according to the regionalization (somatic makes forelimb, flank, and hindlimb, and splanchnic forms stomach, gizzard, small intestine, and large intestine).2.Specification of forelimb/hindlimb identityWe proposed a model that outset of determination to make limb identity is significantly different between forelimb and hindlimb, and that an inhibitory effect plays an important role for this determination (Saito et al., 2002). We further investigated which tissue or region involves the inhibitory factor. Somites at the wing level, implanted into leg region, inhibited the Tbx4 expression in the hindlimb region and induced the Tbx5 expression there. These results suggest that somite may be a source of the inhibitory effect that determines limb identity.3.Fin development of cartilaginous fishesWe have constructed a system to get eggs of cartilaginous fishes continually, and cloned several key genes including Tbx5, Tbx4, Pitxl, shh, fgf8 and msx from two species of cartilaginous fishes, (shark and ray). Especially, existence of Tbx5/4 in cartilaginous fishes strongly suggests that all groups of vertebrates which have limb/fin possess the limb identity regulated by Tbx gene expression (Tamura et al., 2001). Taken together with the expression pattern of msx gene in cartilaginous fishes, we also suggested that flank region between forelimb and hindlimb of cartilaginous fishes has a potential for making limb as well.

1.内脏/躯体侧板的区域化机制我们的外植体研究表明，侧板中胚层，最终分为内脏/躯体层，已经沿着前后轴进行了区域化，他们建议这两层根据区域化指定其前后模式（躯体形成前肢、侧腹和后肢，内脏形成胃、砂囊、小肠，和大肠）。2.前肢规格/后肢同一性我们提出了一个模型，前肢和后肢之间确定肢体同一性的开始是显著不同的，抑制效应对该确定起重要作用（Saito等人，2002年）。我们进一步研究了哪些组织或区域涉及抑制因子。将翼水平的体节植入腿区，抑制后肢区的Tbx 4表达，并诱导后肢区的Tbx 5表达。3.软骨鱼类的鳍发育我们建立了软骨鱼类卵的连续获取系统，并从两种软骨鱼类（鲨鱼和鳐）中克隆了Tbx 5、Tbx 4、Pitx 1、shh、fgf 8和msx等关键基因。特别地，软骨鱼类中Tbx 5/4的存在强烈地表明具有肢/鳍的所有脊椎动物群具有由Tbx基因表达调节的肢身份（Tamura et al.，2001年）。结合msx基因在软骨鱼类中的表达模式，我们也认为软骨鱼类前肢和后肢之间的侧翼区域也具有造肢的潜力。