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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM037193-13
Application #
2690052
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1986-07-01
Project End
2002-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Yuan, Kai; Seller, Charles A; Shermoen, Antony W et al. (2016) Timing the Drosophila Mid-Blastula Transition: A Cell Cycle-Centered View. Trends Genet 32:496-507
Yuan, Kai; O'Farrell, Patrick H (2016) TALE-light imaging reveals maternally guided, H3K9me2/3-independent emergence of functional heterochromatin in Drosophila embryos. Genes Dev 30:579-93
Yuan, Kai; O'Farrell, Patrick H (2015) Cyclin B3 is a mitotic cyclin that promotes the metaphase-anaphase transition. Curr Biol 25:811-816
O'Farrell, Patrick H (2015) Growing an Embryo from a Single Cell: A Hurdle in Animal Life. Cold Spring Harb Perspect Biol 7:
Farrell, Jeffrey A; O'Farrell, Patrick H (2014) From egg to gastrula: how the cell cycle is remodeled during the Drosophila mid-blastula transition. Annu Rev Genet 48:269-94
Yuan, Kai; Shermoen, Antony W; O'Farrell, Patrick H (2014) Illuminating DNA replication during Drosophila development using TALE-lights. Curr Biol 24:R144-5
El Amine, Nour; Kechad, Amel; Jananji, Silvana et al. (2013) Opposing actions of septins and Sticky on Anillin promote the transition from contractile to midbody ring. J Cell Biol 203:487-504
Farrell, Jeffrey A; O'Farrell, Patrick H (2013) Mechanism and regulation of Cdc25/Twine protein destruction in embryonic cell-cycle remodeling. Curr Biol 23:118-26
Kechad, Amel; Jananji, Silvana; Ruella, Yvonne et al. (2012) Anillin acts as a bifunctional linker coordinating midbody ring biogenesis during cytokinesis. Curr Biol 22:197-203
Yuan, Kai; Farrell, Jeffrey A; O'Farrell, Patrick H (2012) Different cyclin types collaborate to reverse the S-phase checkpoint and permit prompt mitosis. J Cell Biol 198:973-80

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