Genome Activation and Regulation of Signaling in the Rapidly Dividing Drosophila Embryo

Citation

Sandler, Jeremy Edward (2017) Genome Activation and Regulation of Signaling in the Rapidly Dividing Drosophila Embryo. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9K935KD. https://resolver.caltech.edu/CaltechTHESIS:05112017-102839369

Abstract

Embryonic development of the fruit fly Drosophila melanogaster is unique among model organisms and animals in general, as rapid and syncytial nuclear divisions characterize the early stages before cell membranes form. These nuclear divisions occur every eight to fifteen minutes, culminating with a 45-minute cell cycle where cell membranes form and the 6000 nuclei become 6000 cells before the embryo undergoes gastrulation. At the beginning of development, maternally deposited transcripts define the major axes of the embryo and control all processes that occur. As the syncytial nuclear cycles slow and nuclei migrate to the periphery of the embryo, maternal transcripts are degraded and the zygotic genome is first activated. The rapid pace of nuclear divisions concurrent with the activation of the zygotic genome presents unique challenges to the developing embryo, as the constraints imposed by mitosis limit the ability to transcribe new genes. This switch of control, the Maternal to Zygotic Transition, has been the subject of studies at the molecular and genetic level for almost 30 years. Here, we use new tools and approaches to study the developing embryo at a time scale not previously achieved. We show how the gene regulatory network along the dorsal-ventral axis, including entire signaling pathways, is activated using time point intervals of 10 minutes. Using mutants, we show the contribution of individual genes in the process of development and the resulting changes in expression levels for the entire network. Finally, we examine the transcription of long genes during the rapid syncytial nuclear cycles, when time constraints limit the ability to transcribe the entire gene. We show how an RNA binding protein regulates the truncation of the transcripts into short isoforms with novel coding sequences, and how these short gene products code for functional proteins that regulate the spatiotemporal activation of key signaling pathways in the embryo.

Thesis Files