TRANSCRIPTIONAL REGULATION OF EARLY PROGENITOR COMPETENCE IN THE DROSOPHIIA CENTRAL NERVOUS SYSTEM by KHOA

Original approval signatures are on file with the Graduate School and the University of Oregon Libraries. Neurogenesis in Drosophila and mammals requires the precise integration of spatial and temporal cues. In Drosophila, embryonic neural progenitors, called neuroblasts, sequentially express the transcription factors Hunchback, Kruppel, Pdml/Pdm2 (Pdm) and Castor as they divide to generate a stereotyped sequence of neuronal and glial progeny. Hunchback is necessary and sufficient to specify the first-born cell identity in many neuroblast lineages. Additionally, Hunchback is able to maintain an early-competence state in which early-born cells are generated. Furthermore, the Hunchback mammalian ortholog, Ikaros, possesses a similar ability to specify early-born cells in the vertebrate nervous system. However, the mechanisms underlying the function of HunchbacklIkaros are unknown. v Pdm and Castor are expressed later in many neuroblasts and can specify late-born neuronal cell identities in a model neuroblast lineage, NB7-1. Previous work studying their function in the .t\TB7-1 lineage showed that Pdm and Castor act as repressors of Kruppel gene expression and inhibit the generation of the Kruppel-dependent cell identity. It is not known if the functions of Pdm and Castor are conserved across multiple neuroblast lineages during neurogenesis or whether these factors impart any restrictions on the ability of a factor like Hunchback to maintain early competence. To investigate the transcriptional mechanisms regulating early neuroblast competence in Drosophila, I have focused my dissertation research on two aims. The first is to examine the function of Pdm and Castor across multiple neuroblast lineages to characterize their potential roles as competence restricting factors; the second is to determine how Hunchback maintains early neuroblast competence and specifies early-born cell identities (e.g. as a transcriptional activator, repressor, or both). My work demonstrates that Pdm and Castor control the timing of Kruppel gene expression, and possibly the timing of other genes, in neuroblasts. Furthermore, I have shown that Hunchback acts as a transcriptional repressor of multiple target genes, including pdm and castor, to maintain early neuroblast competence. Because Hunchback must repress at least one additional unknown factor that can restrict neuroblast competence, I have piloted a screen to identify and characterize novel Hunchback target genes in the nervous system. This dissertation includes previously published and unpublished co-authored materials. (2010). Recombineering Hunchback identifies two conserved domains required to maintain neuroblast competence and specify early-born neuronal identity. Vlll ACKNOWLEDGMENTS I would like to sincerely thank my advisor, Dr. Chris Q. Doe, for all …