Temporal regulation of cell divisions in the embryo of Drosophila melanogaster

Abstract

Cell proliferation is one of the elementary operations involved in building and maintaining the bodies of organisms, and animal development employs diverse regulatory strategies to ensure that it happens in the correct spatial and temporal arrangements. This dissertation is a study of some of the mechanisms involved in timing the early cell cycles of the embryo of Drosophila melanogaster. In chapter 1, we introduce many of the important concepts and provide the reader with background on developmental regulation of the cell cycle. In chapter 2, we turn our focus to the problems associated with the cell-cycle transitions that accompany the maternal-to-zygotic transition. Specifically, it had been shown that slowing of the cell cycle following the initial rapid cleavage divisions is linked to the downregulation of protein phosphatase Cdc25/Twine activity. We pursue this problem with a structure-function analysis of Cdc25/Twine. In chapter 3, we turn our attention to the fourteenth round of cell divisions, which form exquisite spatio-temporal patterns called mitotic domains. Six heterochronic genes (btd, ems, kni, slp1, h, and hkb) had been identified that have dosage-sensitive effects on the timing of cell division in mitotic domain 2 (MD2). We tag two of these factors with GFPs using BAC trangenesis and measure their dynamics in MD2 and other head domains. We find that btd is expressed in a gradient that anticipates the mitotic schedule of MD2, and that slp1 is a powerful repressor of mitosis in the head domains. We conclude that these two factors contribute to the timing of MD2 via a mixed hourglass model that involves both activator-accumulation and repressor-depletion.