Different Notch Receptors in Drosophila Development

描述（由申请人提供）：Notch受体产生不同类型的 在人类发育过程中的分化信号。因此，他们 丧失或异常活动导致不同类型的发育缺陷 和疾病。了解这些疾病的基础，并能够巧妙地 处理每一个问题，我们必须理解所有不同的信号， 由这些受体产生。果蝇提供了一个理想的系统， 目的.在中枢神经系统和表皮的分化过程中， 在果蝇胚胎中，Notch产生四到五种不同类型的信号。 产生的指定表皮前体细胞的信号是良好的， 明白然而，对其他类型的Notch知之甚少 信号、传递信号的细胞内途径或传递信号的机制 它们是生成的。最近的研究表明，全长Notch受体， 初级受体产生两个次级受体， 比主要受体的活性。三人的不同活动 受体一起有可能解释所有不同类型的 由Notch产生的分化信号。拟议的研究将使用 分子遗传学和生物化学分析，以确定以下内容。(1)的 不同Notch受体产生的体内信号的性质 不同的分化阶段。(2)是否有来自 次级受体通过与转导受体相同的途径转导。 表皮前体细胞信号。(3)已知与Notch结合的蛋白质 调节不同受体的产生和活动。这些 研究预计将导致了解如何主要和 二级Notch受体调节组织的分化， 发展

DESCRIPTION (provided by applicant): Notch receptors generate different types of differentiation signals during development of humans. Accordingly, their loss or aberrant activities result in different types of developmental defects and diseases. To understand the basis for these maladies, and be able to deftly deal with each one of them, we must understand all the different signals generated by these receptors. Drosophila offers an ideal system for the purpose. During differentiation of the central nervous system and epidermis in Drosophila embryos, Notch generates four to five different types of signals. The signals generated to specify the epidermal precursor cells are well understood. However, very little is known about the other types of Notch signals, the intracellular pathways transducing them, or the mechanism by which they are generated. Recent studies show that the full-length Notch receptor, the primary receptor, generates two secondary receptors showing different activities than the primary receptor. The different activities of the three receptors together have the potential to account for all the different types of differentiation signals generated by Notch. The proposed studies will use molecular genetic and biochemical analyses to determine the following. (1) The nature of in vivo signals generated by the different Notch receptors at different stages of differentiation. (2) Whether or not signals from the secondary receptors are transduced by the same pathway that transduces the epidermal precursor cell signals. (3) Whether proteins known to bind Notch regulate the production and activities of the different receptors. These studies are expected to lead to an understanding of how the primary and secondary Notch receptors regulate differentiation of tissues during development.