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

中枢神经系统（CNS）是一个由许多不同的神经元组成的复杂网络，能够以惊人的保真度传递电化学信号。在发育中的中枢神经系统中，神经元细胞命运的获得是一个高度调控的，但进化保守的过程。研究支持这样的假设，即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的表达。例如，已知的转录因子组合指定运动神经元轴突腹侧的身份，而不同的组合指定运动神经元轴突背侧的身份。运动神经元的每个亚类都延伸轴突来支配不同的肌肉目标。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新发现的神经元规范调节因子，果蝇转录因子基因neurromancer2 （nmr2）。到目前为止，Nmr2蛋白与已知的指定运动神经元和中间神经元命运的转录因子之间的表达研究表明，这些因子之间的共表达很少。因此，该项目的第一个目标是采用遗传筛选来识别与nmr2相互作用的基因。鉴定nmr2相互作用基因将解析nmr2的功能，并确定nmr2是否是控制神经元规范的新型转录因子组合代码成员。第二个目标是确定Nmr2介导其对神经元特异性影响的下游基因靶点。将遗传学和胚胎学方法与全基因组搜索Nmr2转录因子基因靶点相结合，将阐明Nmr2如何指导不同的神经元相互分化。进一步的比较分析将有助于了解Tbx20的功能，Tbx20是nmr2的保守的哺乳动物对应物。此外，该项目将为本科生和研究生提供科学培训机会，以完成研究论文，共同撰写手稿，并在科学会议上展示他们的研究成果。这个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在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.