RIG: Identification of the Drosophila Tbx20 transcription factor regulatory network mediating neuronal specification

中枢神经系统（CNS）是一个复杂的网络，许多不同的神经元能够中继电化学信号具有显着的保真度。 发育中的CNS内神经元细胞命运的获得是高度调节的，但在进化上保守的过程。 研究支持了核转录因子结合蛋白的独特组合激活和/或抑制神经元命运决定基因表达的假设。 例如，已知的转录因子组合指定腹侧投射轴突的运动神经元的身份，而不同的组合指定背侧投射轴突的运动神经元的身份。 运动神经元的每个亚类延伸轴突以支配不同的肌肉靶点。 为了解码指定神经元命运的转录因子网络，拟议的研究将在功能上表征一个新发现的神经元规格调节器，果蝇转录因子基因neuromancer 2（nmr 2）。 到目前为止，Nmr 2蛋白和转录因子之间的表达研究，已知指定运动神经元和中间神经元的命运揭示这些因素之间的共表达很少。 因此，本项目的第一个目标是采用遗传筛选来鉴定与nmr 2相互作用的基因。 识别nmr 2相互作用的基因将解决nmr 2的功能，并确定nmr 2是否是一个新的转录因子组合编码成员管理的规范神经元。 第二个目标是确定Nmr 2介导其对神经元特异性的影响的下游基因靶点。 遗传学和胚胎学方法与全基因组搜索Nmr 2转录因子基因靶点的整合将阐明Nmr 2如何指导不同的神经元组相互分化。 进一步的比较分析将提供深入了解Tbx 20的功能，保守的哺乳动物nmr 2的对应物。 此外，该项目将为本科生和研究生提供科学培训机会，以进行研究论文，共同撰写手稿，并在科学会议上介绍他们的研究。 该项目将在密西西比大学进行。 因此，该项目有可能扩大少数民族学生对STEM学科的参与。

The central nervous system (CNS) is an elaborate network of many diverse neurons capable of relaying electrochemical signals with remarkable fidelity. The acquisition of neuronal cell fates within the developing CNS is a highly regulated, yet evolutionarily conserved process. Research supports the hypothesis that a distinct combination of nuclear transcription factor binding proteins activates and/or inhibits the expression of neuronal fate determination genes. For example, a known combination of transcription factors specifies the identity of motor neurons projecting axons ventrally, while a different combination specifies the identity of motor neurons projecting axons dorsally. Each subclass of motor neurons extends axons to innervate different muscle targets. To decode the transcription factor networks specifying neuronal fates, the proposed research will functionally characterize a newly identified regulator of neuronal specification, the Drosophila transcription factor gene neuromancer2 (nmr2). Thus far, expression studies between Nmr2 proteins and transcription factors known to specify motor neuron and interneuron fates reveal little co-expression between these factors. Consequently, the first goal of this project is to employ a genetic screen to identify genes that interact with nmr2. Identifying nmr2-interacting genes will resolve nmr2 function and determine whether nmr2 is a novel transcription factor combinatorial code member governing the specification of neurons. The second goal is to define the downstream gene targets through which Nmr2 mediates its effects on neuronal specification. The integration of genetics and embryological methods with genome-wide searches for Nmr2 transcription factor gene targets will elucidate how Nmr2 directs distinct sets of neurons to differentiate from each other. Further comparative analyses will provide insight to understand the function of Tbx20, the conserved mammalian counterpart of nmr2. In addition, this project will provide scientific training opportunities for undergraduate and graduate students to pursue a research thesis, to co-author manuscripts, and to present their research at scientific meetings. This project will be conducted at the University of Mississippi. As such the project has the potential to broaden participation of minority students in STEM disciplines.