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New molecular concepts on pattern formation in limb morphogenesis.

关于肢体形态发生中模式形成的新分子概念。

基本信息

批准号：
17370076
负责人：
TAMURA Koji
金额：
$ 9.34万
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：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17370076/
关键词：
limb development morphogenesis gene expression fin organ formation patterning

项目摘要

In terms of the anterior-posterior axis formation in a developing limb bud, a gene, mario, which has unique expression pattern in the limb bud, has a crucial role in the antero-posterior patterning, and a part of the molecular cascade for the patterning, including mario and bmp, was identified. Also, digit number in Xenopus forelimb is identified as not 1234 but 2345 by expression analysis of HoxD genes.In terms of the proximal-distal axis formation in the limb bud, a detailed fate map showed that future autopod region and future zeugopod region is largely overlapped in an early limb bud, but that the overlap is getting smaller as the development proceeds. Hoxa13/Hoxall expression profile confirmed these results from the fate map. Also, the expression analysis revealed that the molecular condition in the distal limb bud is changing progressively.A series of transplantation experiments suggested that a factor(s) from the axial structure, somites determines limb-type identity. Transplantation of different level of somites induced transition of Tbx4/5 expression and inhibited outgrowth of the hindlimb bud. These results suggest that positioning of limb field and its identity are specified not in an autonomous manner in the lateral plate mesoderm but that the tissue-tissue interactions are important.Epigenetic regulation of shh expression was examined, and the results indicated a well correlation between shh expression and DNA methylation of shh enhancer sequence (shh-expressing tissues had low condition of DNA methylation in the enhancer region), suggesting that epigenetic control of shh enhancer region plays a role in shh expression during limb development and regeneration.

根据发育中肢芽前后轴的形成，mario基因在肢芽中具有独特的表达模式，在前后图式形成中起着关键作用，并确定了包括mario和bmp的图式形成分子级联的一部分。此外，通过HoxD基因的表达分析，爪蟾前肢的趾数不是1234，而是2345。在肢芽中近端-远端轴的形成方面，详细的命运图显示，在早期肢芽中，未来的autopod区域和未来的zeugopod区域在很大程度上重叠，但随着发育的进行，重叠越来越小。Hoxa 13/Hoxall表达谱证实了来自命运图的这些结果。此外，表达分析还表明，远侧肢芽的分子状态正在发生变化，一系列移植实验表明，来自轴向结构的一个因子，体节决定了肢型的同一性。移植不同水平的体节诱导Tbx 4/5表达的转变，抑制后肢芽的生长。这些结果表明，肢野的定位及其身份在侧板中胚层中不是以自主的方式被指定的，而是组织-组织相互作用是重要的。研究了shh表达的表观遗传调控，结果表明shh表达与shh增强子序列的DNA甲基化有很好的相关性（shh表达组织在增强子区域具有低的DNA甲基化条件），表明shh增强子区域的表观遗传控制在肢体发育和再生期间的shh表达中起作用。