The Role of Numb in Lymphocyte Development

描述（由申请人提供）：Notch是一种跨膜受体， 在从果蝇到人类的各种生物体中的细胞命运决定中。 最近，通过Notch的信号传导已经被牵连到多个细胞的命运 决定淋巴细胞的发育。尽管有证据支持 Notch，Notch活性在淋巴细胞发育过程中如何调节， 知道的与Notch调控有关的蛋白质之一是Numb。麻木 是一种衔接蛋白，它与Notch结合并抑制其活性。主要 该建议的目的是研究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Numb的过表达和显性负性形式的 T细胞谱系测定中的麻木。具体目标2将测试的效果 使用胸腺细胞在体内确定T细胞谱系中的Numb缺陷 特定条件性Numb敲除。最后，具体目标3将测试角色 在B与T细胞谱系测定中NumB。

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.