NOTCH SIGNALING AND VERTEBRATE LIMB DEVELOPMENT

描述(改编自研究人员摘要)：在脊椎动物 胚胎发生模式信号来自非常离散的中心，如 亨森结节，中脑-后脑交界处，或者在肢体的情况下， 顶端外胚层脊的极化活动区(ZPA)。 很明显，许多控制发育的分子 昆虫的通路在脊椎动物中也有类似的通路。AER是 脊椎动物肢体生长所必需的。海脊的形成依赖于 先前建立的背侧-腹侧肢轴。调查员 已经克隆了一个基因r-fng，它在背部外胚层和 山脊。异位表达实验表明，r-FNG能够 诱导更多的AER表明AER是从 在非组织旁高水平表达r-FNG，即r-FNG 边界。在果蝇中也提出了类似的机制，在那里 FNG基因在翅膀发育过程中起着关键作用。身份识别 存在一个共同的信号传递过程，它调节了 果蝇的翼缘和脊椎动物的AER将会相当令人惊讶，甚至 根据先前证明的两个系统发育之间的同源性 这将需要分离下游分子。在……里面 果蝇，FNG的激活诱导了一系列事件，导致 Serrate、Notch、Fresgial、Cut和His基因表达的激活 背腹交界处无翅。调查员克隆了一只小鸡 Serrate、Notch和Cut的同源物并显示它们在 阿尔。通过使用野生型和肢体突变胚胎，研究人员将 研究中断Notch信令对建立和 定位脊椎动物AER。上述分子也是 在胚胎发生过程中所需的其他过程，如神经发生和 体细胞发生。这表明在肢体发育过程中，体细胞发生， 或神经发生，类似的遗传构建块组合可能是 一次又一次地使用。了解这些基因砖相互作用的方式 为了定位和建立AER将被证明是 一个有价值的企业，不仅从肢体发展的角度来看， 但也是从更广泛的角度来解开进化是如何 利用相同的分子组合来建立其他信号 是脊椎动物发育的中心。

DESCRIPTION (adapted from investigator's abstract): During vertebrate embryogenesis patterning signals emanate from very discrete centers like the Hensen's node, the midbrain-hindbrain junction or, in the case of the limb, the zone of polarizing activity (ZPA) of the apical ectodermal ridge (AER). It has become evident that many of the molecules that control developmental pathways in insects have homologous counterparts in vertebrates. The AER is required for vertebrate limb outgrowth. Formation of the ridge relies on the previous establishment of the dorso-ventral limb axis. The investigator has cloned a gene, r-fng, which is expressed in the dorsal ectoderm and in the ridge. Ectopic expression experiments indicate that r-fng is able to induce additional AERs suggesting that the AER develops from tissue that is expressing high levels of r-fng adjacent to tissue that is not, i.e. a r-fng boundary. A similar mechanism has been proposed in Drosophila, where the fng gene plays a pivotal role in wing development. Identification of the existence of a common signaling process that mediates the formation of the Drosophila wing margin and the vertebrate AER will be quite surprising, even in light of previously demonstrated homologies between the two phylogenetic groups, and it will require the isolation of downstream molecules. In Drosophila, activation of fng induces a cascade of events that results in the activation of the expression of Serrate, Notch, Vestigial, Cut and Wingless at the dorso-ventral boundary. The investigator has cloned chick homologues of Serrate, Notch and Cut and shown they are expressed in the AER. By using wild type and limb mutant embryos, the investigator will study the consequences of disrupting Notch signaling for establishing and positioning the vertebrate AER. The molecules described above are also required during embryogenesis for other processes like neurogenesis and somitogenesis. This suggests that during limb development, somitogenesis, or neurogenesis, a similar combination of genetic building blocks could be used again and again. Understanding the way these genetic bricks interact with each other in order to position and establish the AER will prove to be a rewarding enterprise, not only from the point of view of limb development, but also from a more general perspective of unraveling how evolution has utilized the same combination of molecules to establish other signaling centers during vertebrate development.