DEVELOPMENTAL PROGRAMS OF CELL CYCLE CONTROL

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The control of cell proliferation is important for embryonic development and tissue stability in the adult, where erosion of constrains on the cell cycle leads to disease. Early embryonic cell are specialized to multiply rapidly, which they do to the exclusion of movement, transcription and even the compaction of DNA into heterochromatin. The sequential addition of cell cycle constrains tames the rampant proliferation of early development and prepares the embryo for gene expression, morphogenesis and differentiation. In Drosophila, S phase lengthens as transcription begins, a G2 phase is added to the cell cycle at the time gastrulation movements begin, and a G1 phase is added prior to cellular differentiation. We will investigate the mechanisms that govern the cell cycle as it is successively transformed and the impact of these transformation on events underlying gene expression and morphogenesis. We will do this in Drosophila, which offers a well characterized model developmental system having powerful genetic, molecular and cytological tools. Changes in expression or degradation of the cell cycle regulators accompany the cell cycle transitions. For example, the mitotic cyclins are continuously present in the early cycles which have only S and M phases. They are destroyed at mitosis upon the introduction of a G2, and their post mitotic re-accumulation is delayed upon introduction of a G1. They are completely eliminated in endocycles. We will investigate how this diversity of cyclin behaviors alters the roles of the cyclins in controlling exit from mitosis, and in preventing re-replication. To explore the coordination of the cell cycle with morphogenesis, we will examine controls that delay mitosis in cells involved in ventral furrow formation: without this delay, mitosis disrupts furrow formation. To investigate the role of cell cycle lengthening in gene expression, we are testing whether a DNA sequence can be simultaneously transcribed and replicated, and we are investigating the cell cycle coupling of the appearance of heterochromatin which contributes to stable inactivation of gene expression.