A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling.
A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling.
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发表时间：
2000-04
期刊：
影响因子：
4.6
通讯作者：
G. Drossopoulou;K. Lewis;J. Sanz-Ezquerro;N. Nikbakht;A. McMahon;C. Hofmann;C. Tickle
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文献类型：
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作者：
G. Drossopoulou;K. Lewis;J. Sanz-Ezquerro;N. Nikbakht;A. McMahon;C. Hofmann;C. Tickle
有人提出，鸡肢芽中的数字身份是由极化区产生的长程形态发生素以剂量依赖的方式指定的。一个候选者是Sonic hedgehog（Shh）蛋白，但尚不清楚Shh是长距离还是短距离，还是通过Bmps起作用。在这里，我们剖析了Shh和Bmp信号之间的关系。我们表明，嘘是必要的，不仅启动BMP 2的表达，但也维持其表达期间，额外的数字被指定。我们还表明，我们可以重现Shh在此期间只应用Bmp2的效果。我们进一步证明，它是BMPs负责数字规格通过瞬时添加头蛋白或BMP抗体与Shh处理的肢体。在这样的肢体中，多个额外的手指仍然形成，但它们都具有相同的身份。我们还探讨了时间依赖性和范围的Shh信号通过检查PTC表达。我们发现，高水平的PTC表达诱导迅速时，无论是嘘珠或极化区域移植到主机肢体。此外，我们发现，高水平的ptc表达是广泛的，但后来更多的限制。所有这些数据使我们提出了一个新的数字模式。我们认为，嘘最初的行为范围长，以总理的肢体主管，形成数字，从而控制数字的数量。然后，Shh作用于短距离诱导Bmps的表达，其形态发生作用指定手指身份。
It has been proposed that digit identity in chick limb bud is specified in a dose-dependent fashion by a long-range morphogen, produced by the polarising region. One candidate is Sonic hedgehog (Shh) protein, but it is not clear whether Shh acts long or short range or via Bmps. Here we dissect the relationship between Shh and Bmp signalling. We show that Shh is necessary not only for initiating bmp2 expression but also for sustaining its expression during the period when additional digits are being specified. We also show that we can reproduce much of the effect of Shh during this period by applying only Bmp2. We further demonstrate that it is Bmps that are responsible for digit specification by transiently adding Noggin or Bmp antibodies to limbs treated with Shh. In such limbs, multiple additional digits still form but they all have the same identity. We also explored time dependency and range of Shh signalling by examining ptc expression. We show that high-level ptc expression is induced rapidly when either Shh beads or polarising regions are grafted to a host limb. Furthermore, we find that high-level ptc expression is first widespread but later more restricted. All these data lead us to propose a new model for digit patterning. We suggest that Shh initially acts long range to prime the region of the limb competent to form digits and thus control digit number. Then later, Shh acts short range to induce expression of Bmps, whose morphogenetic action specifies digit identity.