CELL INTERACTIONS ORGANIZING THE INSECT SEGMENT

Hedgehog（Hh）家族的分泌蛋白介导多种短- 果蝇发育过程中的细胞信号事件， 脊椎动物这项研究的长期目标是了解 Hh信号转导及其与其他细胞过程的整合。 Hb被认为是一种形态发生素，具有特定的Hh水平 指定唯一响应的信号。这项工作的主要目标是 确定不同水平的Hh信号传导如何定性地导致 不同的反应。最近的遗传和分子证据支持 Smoothened（Smo）的参与，一种假定的七跨膜（7-TM） Hh受体。这项研究使用体内细胞， 培养和生物化学方法来探讨Smo在Hh中的作用 发信号。四个具体目标概述了该提案： 1)Hh和Smo之间的物理相互作用试验， 2)检测异源三聚体G蛋白参与Hh信号传导， 3)检测另一种细胞表面蛋白Patched对Smo的调节， 和 4)蛋白激酶A对Smo的调节试验。 这些实验将探讨Smo在Hh信号中的作用和调控 转导由此产生的对Smo调节的描述可能具有 在更广泛的背景下，7-TM受体介导的 生理学和生物学。Hh信号控制着关键神经元的产生， 这些人口因脊髓灰质炎和帕金森氏症等疾病而减少。 了解Hh信号传导可能会导致预防Hh的策略。 失去或替换这些神经群体。

The Hedgehog (Hh) family of secreted proteins mediates a variety of short- range cell signalling events in development of Drosophila and several vertebrates. The long term objectives of this research are to understand Hh signal transduction and its integration with other cellular processes. Hb has been proposed to act as a morphogen, with specific levels of Hh signal specifying unique responses. The principal goal of the work is to determine how different levels of Hh signaling lead to qualitatively different responses. Recent genetic and molecular evidence supports the involvement of Smoothened (Smo), a putative seven transmembrane (7-TM) receptor, as a Hh receptor. The proposed research uses in vivo, cell culture, and biochemical approaches to explore the role of Smo in Hh signaling. Four Specific Aims outline the proposal: 1) Test for physical interaction between Hh and Smo, 2) Test for participation of heterotrimeric G proteins in Hh signaling, 3) Test for regulation of Smo by Patched, another cell surface protein, and 4) Test for regulation of Smo by Protein Kinase A. These experiments will explore the role and regulation of Smo in Hh signal transduction. The resulting description of Smo regulation could have profound implications in the broader context of 7-TM receptor-mediated physiology and biology. Hh signaling controls the generation of key neural populations which are depleted in diseases such as polio and Parkinson's. Understanding Hh signaling could lead to strategies for preventing the loss of or for replacing these neural populations.