The Role of Numb in Lymphocyte Development

描述(申请人提供)：Noch是一种参与的跨膜受体 在从果蝇到人类的各种生物中，细胞命运的决定。 最近，通过Notch发出的信号与多个细胞的命运有关 淋巴细胞发育的决定。尽管有证据支持 Notch，Notch活性在淋巴细胞发育过程中是如何调节的 为人所知。参与Notch调控的蛋白质之一是Numb。数字 是一种与Notch结合并抑制其活性的适配蛋白。少校 这项建议的目的是研究Numb在淋巴细胞发育中的作用。 为了实现这一点，我们将使用几种互补的方法。具体目标1 将测试数字过度表达的效果和显性否定形式 Numb在T细胞谱系测定中的应用。《特定目标2》将测试 胸腺细胞体内T细胞谱系测定中的Numb缺乏 特定条件数字淘汰赛。最后，《特定目标3》将测试这一角色 B细胞与T细胞谱系测定中Numb的比例。

DESCRIPTION (provided by applicant): Notch is a transmembrane receptor involved in cell fate decisions in diverse organisms ranging from Drosophila to humans. Recently, signaling through Notch has been implicated in multiple cell fate decisions in lymphocyte development. Despite the evidence supporting a role for Notch, how Notch activity is regulated during lymphocyte development is not known. One of the proteins implicated in the regulation of Notch is Numb. Numb is an adapter protein that binds to Notch and inhibits its activity. The major aim of this proposal is to examine the role of Numb in lymphocyte development. To achieve this we will use several complementary approaches. Specific aim 1 will test the effect of overexpression of Numb and a dominant negative form of Numb in T cell lineage determination. Specific Aim 2 will test the effect of Numb deficiency in T cell lineage determination in vivo using a thymocyte specific conditional Numb knockout. Lastly, specific Aim 3 will test the role of Numb in B versus T cell lineage determination.