This is a MERIT Extension application Request: The goal of this research is to define the cellular and molecular mechanisms responsible for morphological transitions that occur during embryogenesis. Our experiments focus on cycle 14 in Drosophila because the changes that occur at that stage (cellularization and gastrulation) are rapid, simple and reproducible, and can be easily visualized using molecular markers for cytoskeletal and cell adhesion components. Cycle 14 also defines the stage in Drosophila development when the embryo transitions from a complete dependence on maternally supplied gene products to a reliance on zygotic transcription. It thus offers unique genetic advantages for Identifying genes that are relevenat for these processes. Our work is specifically directed at the genes and mechanisms that control cell cycle behavior, global transcription and morphological change. In the next five years, we will continue our analysis of these processes using confocal microscopy of living embryos, classical genetics, molecular biology, quantitative imaging and computer based modeling. Our analysis of cell cycle changes at cycle 14 will focus on String and Twine, two cdc25 homologues that are supplied maternally and whose degradation at cycle 14 appeared to govern the pause in cell cycle that occurs at that time. We will also use chromosomal rearrangements to generate embryos that are missing defined regions of the genome and use the phenotypes observed in those embryos to identify genes that are active at that time. Our initial analysis will focus on the gene or genes located in the centromeric regions of the heterochromatin that are essential for the final fast phase of cellularization. We will investigate the mechanism that control cell shape change in mesodermal cells at the onset of gastrulation, using quantitative imaging and cell reconstructions to analyze the organization of the actin-myosin cytoskeleton and the apical constrictions that occurs in those cells. We will extend this approach to other morphogenetic events of gastrulation.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Coulombe, James N
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Princeton University
Schools of Arts and Sciences
United States
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Weng, Mo; Wieschaus, Eric (2017) Polarity protein Par3/Bazooka follows myosin-dependent junction repositioning. Dev Biol 422:125-134
Falahati, Hanieh; Wieschaus, Eric (2017) Independent active and thermodynamic processes govern the nucleolus assembly in vivo. Proc Natl Acad Sci U S A 114:1335-1340
He, Bing; Martin, Adam; Wieschaus, Eric (2016) Flow-dependent myosin recruitment during Drosophila cellularization requires zygotic dunk activity. Development 143:2417-30
Blythe, Shelby A; Wieschaus, Eric F (2016) Establishment and maintenance of heritable chromatin structure during early Drosophila embryogenesis. Elife 5:
Weng, Mo; Wieschaus, Eric (2016) Myosin-dependent remodeling of adherens junctions protects junctions from Snail-dependent disassembly. J Cell Biol 212:219-29
Falahati, Hanieh; Pelham-Webb, Bobbie; Blythe, Shelby et al. (2016) Nucleation by rRNA Dictates the Precision of Nucleolus Assembly. Curr Biol 26:277-85
Blythe, Shelby A; Wieschaus, Eric F (2015) Zygotic genome activation triggers the DNA replication checkpoint at the midblastula transition. Cell 160:1169-81
Polyakov, Oleg; He, Bing; Swan, Michael et al. (2014) Passive mechanical forces control cell-shape change during Drosophila ventral furrow formation. Biophys J 107:998-1010
He, Bing; Doubrovinski, Konstantin; Polyakov, Oleg et al. (2014) Apical constriction drives tissue-scale hydrodynamic flow to mediate cell elongation. Nature 508:392-6
Di Talia, Stefano; Wieschaus, Eric F (2014) Simple biochemical pathways far from steady state can provide switchlike and integrated responses. Biophys J 107:L1-L4

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