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

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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.