The role of transcription factors in Drosophila neurodevelopment

Animal development depends on the interplay between intercellular signaling and gene expression, which is regulated by transcription factors. In Drosophila, the transcription factors Achaete (Ac) and Scute (Sc) are part of a feedback loop with the Notch (N) receptor signaling pathway. This loop results in the specification of a single sensory organ precursor (SOP) from a field of neurally-competent cells. Within the SOP, Ac and Sc promote the Delta (Dl) signal, which activates N to repress ac and sc expression (and neural fate) in cells neighboring the SOP. Although the framework of this loop has been described, it is not known what factors Ac and Sc interact with within the SOP, or which genes downstream of Ac and Sc promote Dl signaling. It is also unclear how the SOP is committed to its neural fate after it is specified.; nervy (nvy) is the Drosophila homolog of the mammalian proto-oncogene ETO and is expressed in the differentiating SOP. nvy gain- and loss-of-function experiments indicate that nvy interacts with both daugtherless (da), which encodes an Ac and Sc DNA-binding partner protein, and N. Based on these data and others, I propose a model in which nvy acts downstream of ac and sc to amplify the Dl signal emanating from the SOP.; In humans, the most common chromosomal aberration associated with acute myelogenous leukemia is the t(8;21) translocation, which fuses ETO with AML1. The resulting AML1-ETO chimera is hypothesized to interfere with the function of endogenous AML1, which is necessary for hematopoiesis. Here, I use the Drosophila eye as a model system to investigate how the AML1-ETO chimera functions, supporting a model in which AML1-ETO acts as a constitutive repressor.; The Drosophila homolog of AML1, lozenge (lz), encodes a transcription factor that has been previously shown to promote cell differentiation in the larval eye disc. lz is also expressed in the pupal retina, suggesting lz has additional functions during eye development. Removing Lz during pupal stages results in a decrease in apoptosis. A search for Lz binding sites identified putative enhancers in two genes, argos ( aos) and klumpfuss (klu), both of which encode antagonists of the anti-apoptotic Epidermal Growth Factor Receptor (EGFR). Additional experiments demonstrated that Lz directly activates the expression of aos and klu.