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Determination of positional identity during limb development and regeneration

肢体发育和再生过程中位置同一性的确定

基本信息

批准号：
10680692
负责人：
NOHNO Tsutomu
金额：
$ 1.98万
依托单位：
KAWASAKI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

Roles of signaling molecules in determination of positional information have been studied in the developing and regenerating limb, and the results are summarized below.Wnt-5a expressed in the distal limb bud at early stage of development was over-expressed in the chick embryo using retrovirus vector, resulting in shortening of zeugopod length. Wnt family other than Wnt-3a is implicated in induction of the apical ectodermal ridge, and Wnt-10a is a candidate because of expression pattern both in the mouse and chick embryos. However, Wnt-10a was also unable to induce FGF-8 expression when misexpressed in the presumptive limb ectoderm.A novel frizzled family member, Fz-10, was identified in the chick embryo that expressed in the dorsal- posterior region of the limb mesenchyme. Fz-10 was positively regulated by both sonic hedgehog (SHH) and Wnt-7a, and shown to have an activity to mediate Wnt-7a signaling, but not Wnt-3a signaling, as demonstrated by Xenopus animal cap assay.Signaling throu … More gh GPI-anchored cell surface proteins was shown to determine proximal-distal positional value in the limb bud, as demonstrated by cell sorting assay. One of the proteins, ephrin-A2, is expressed in the proximal limb bud, whereas a receptor for ephrin-A, EphA4, is expressed in the distal limb bud with a complementary pattern. Misexpression of ephrin-A2 in the distal limb bud resulted in malformation and partial fusion of the limb cartilage within the autopod region. Limb mesenchymal cells over-expressing ephrin-A2 are segregated from non-expressing cells, suggesting involvement of ephrin-Eph interaction in position-dependent cell adhesion.SHH protein-induced digit duplication is correlated with persistent expression of HoxD12 and HoxD13, but not with transient induction of BMP-2. In the leg bud, FGF-4 could induce SHH expression in the anterior limb bud, thereby up-regulating HoxD13 expression, independent of cell migration from the body flank region. On the contrary, FGF-4 could not induce SHH expression in the wing bud, suggesting differential responsiveness to FGF signaling between the forelimb and hindlimb buds. Less

在肢体发育和再生过程中，信号分子在决定位置信息中的作用已被研究，结果总结如下：利用逆转录病毒载体，在发育早期的远肢芽中表达的Wnt-5a在鸡胚中过表达，导致zeugopod长度缩短。除了Wnt-3a之外的Wnt家族参与了顶端外胚层嵴的诱导，并且Wnt-10a是候选者，因为其在小鼠和鸡胚胎中的表达模式。然而，Wnt-10a在假定的肢体外胚层中错误表达时也不能诱导FGF-8的表达。在鸡胚中鉴定出一种新的卷曲家族成员Fz-10，其在肢体间充质的背后部区域表达。Fz-10受音刺猬（SHH）和Wnt-7a的正调控，并显示具有介导Wnt-7a信号传导的活性，但不介导Wnt-3a信号传导，如爪蟾动物帽分析所示。 ...更多信息 GH GPI锚定的细胞表面蛋白被证明可以确定肢芽中的近端-远端位置值，如细胞分选测定所证明的。其中一种蛋白质ephrin-A2在近端肢芽中表达，而ephrin-A的受体EphA 4在远端肢芽中以互补模式表达。ephrin-A2在远侧肢芽中的错误表达导致肢软骨在自足区域内的畸形和部分融合。肢间充质细胞过度表达ephrin-A2与非表达细胞分离，表明ephrin-Eph相互作用参与位置依赖性细胞adhesion.SHH蛋白诱导的手指重复与HoxD 12和HoxD 13的持续表达相关，但与BMP-2的瞬时诱导无关。在腿芽中，FGF-4可以诱导前肢芽中的SHH表达，从而上调HoxD 13的表达，而不依赖于体侧区域的细胞迁移。相反，FGF-4不能诱导翅芽中SHH的表达，表明前肢和后肢芽对FGF信号传导的反应不同。少