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Transcriptional regulation of early progenitor competence in the Drosophila central nervous system

xiii, 104 p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / 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 firstborn 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 Hunchback/Ikaros are unknown.

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 NB7-1 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. / Committee in charge: Victoria Herman, Chairperson, Biology;
Christopher Doe, Advisor, Biology;
Judith Eisen, Advisor, Biology;
Charles Kimmel, Member, Biology;
Hui Zong, Member, Biology;
Kenneth Prehoda, Outside Member, Chemistry

Identiferoai:union.ndltd.org:uoregon.edu/oai:scholarsbank.uoregon.edu:1794/11302
Date09 1900
CreatorsTran, Khoa Dang, 1983-
PublisherUniversity of Oregon
Source SetsUniversity of Oregon
Languageen_US
Detected LanguageEnglish
TypeThesis
RelationUniversity of Oregon theses, Dept. of Biology, Ph. D., 2010;

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