Posttranslational Control of Cdc25 Degradation Terminates Drosophila's Early Cell-Cycle Program.
ABSTRACT In most metazoans, early embryonic development is characterized by rapid mitotic divisions that are controlled by maternal mRNAs and proteins that accumulate during oogenesis . These rapid divisions pause at the midblastula transition (MBT), coinciding with a dramatic increase in gene transcription and the degradation of a subset of maternal mRNAs [2, 3]. In Drosophila, the cell-cycle pause is controlled by inhibitory phosphorylation of Cdk1, which in turn is driven by downregulation of the activating Cdc25 phosphatases [4, 5]. Here, we show that the two Drosophila Cdc25 homologs, String and Twine, differ in their dynamics and that, contrary to current models , their downregulations are not controlled by mRNA degradation but through different posttranslational mechanisms. The degradation rate of String protein gradually increases during the late syncytial cycles in a manner dependent on the nuclear-to-cytoplasmic ratio and on the DNA replication checkpoints. Twine, on the other hand, is targeted for degradation at the onset of the MBT through a switch-like mechanism controlled, like String, by the nuclear-to-cytoplasmic ratio, but not requiring the DNA replication checkpoints. We demonstrate that posttranslational control of Twine degradation ensures that the proper number of mitoses precede the MBT.
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ABSTRACT: Transcriptional regulation of gene expression is fundamental to most cellular processes, including determination of cellular fates. Quantitative studies of transcription in cultured cells have led to significant advances in identifying mechanisms underlying transcriptional control. Recent progress allowed implementation of these same quantitative methods in multicellular organisms to ask how transcriptional regulation unfolds both in vivo and at the single molecule level in the context of embryonic development. Here we review some of these advances in early Drosophila development, which bring the embryo on par with its single celled counterparts. In particular, we discuss progress in methods to measure mRNA and protein distributions in fixed and living embryos, and we highlight some initial applications that lead to fundamental new insights about molecular transcription processes. We end with an outlook on how to further exploit the unique advantages that come with investigating transcriptional control in the multicellular context of development.Trends in Genetics 07/2014; · 11.60 Impact Factor
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ABSTRACT: While cell proliferation is an essential part of embryonic development, cells within an embryo cannot proliferate freely. Instead, they must balance proliferation and other cellular events such as differentiation and morphogenesis throughout embryonic growth. Although the G 1 phase has been a major focus of study in cell cycle control, it is becoming increasingly clear that G 2 regulation also plays an essential role during embryonic development. Here we discuss the role of Cdc25, a key regulator of mitotic entry, with a focus on several recent examples that show how the precise control of Cdc25 activity and the G 2/M transition are critical for different aspects of embryogenesis. We finish by discussing a promising technology that allows easy visualization of embryonic and adult cells potentially regulated at mitotic entry, permitting the rapid identification of other instances where the exit from G 2 plays an essential role in development and tissue homeostasis.Cell cycle (Georgetown, Tex.) 06/2014; 13(14). · 5.24 Impact Factor
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ABSTRACT: The initial phases of embryonic development occur in the absence of de novo transcription and are instead controlled by maternally inherited mRNAs and proteins. During this initial period, cell cycles are synchronous and lack gap phases. Following this period of transcriptional silence, zygotic transcription begins, the maternal influence on development starts to decrease, and dramatic changes to the cell cycle take place. Here, we discuss recent work that is shedding light on the maternal to zygotic transition and the interrelated but distinct mechanisms regulating the onset of zygotic transcription and changes to the cell cycle during early embryonic development.Development 10/2014; 141(20):3834-3841. · 6.27 Impact Factor