Initiation of embryonic development requires a rapid transition from the resting state in the oocyte to the high divisional activity of the zygote. This transition is packed with important events: activation of the oocyte nucleus to complete meiosis to form a female pronucleus, reorganization of the sperm nucleus into a male pronucleus, coordination of pronuclear division cycles, co-mingling of the genetic material derived from the egg and the sperm, and initiation of rapid mitotic divisions. As crucial as this developmental transition is, its mechanisms and events are poorly understood. We propose to continue studies of YA, a Drosophila nuclear lamina protein essential for the formation and proper behavior of pronuclei. Ya is one of the very few genes identified thus far that act specifically at this critical developmental time. Thus, our studies will provide insight into the initiation of development, as well as into the role of the nuclear lamina in developmental events. To pinpoint the precise events that require YA we will examine in real time the behavior of GFP-labeled chromosomes and spindles in YA mutants. We will also determine whether a nuclear lamina forms between meiosis I and II, and whether Ya regulates if formation. To determine how Ya carries out its function, we will continue to analyze YA's interactions with its macromolecular partners, which include lamin, chromatin, and 4 proteins isolated from a YA-affinity column, including AP3, a DNA repair enzyme. We will use genetic and biochemical tests to determine the biological significance of these interactions. Finally, we will elucidate the developmental controls that permit YA to enter nuclei upon egg activation, and the signals that target YA to the nuclear lamina.
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