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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD015587-32
Application #
8677605
Study Section
No Study Section (in-house review) (NSS)
Program Officer
Coulombe, James N
Project Start
1981-08-01
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
32
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Princeton
State
NJ
Country
United States
Zip Code
08543
Blythe, Shelby A; Wieschaus, Eric F (2016) Establishment and maintenance of heritable chromatin structure during early Drosophila embryogenesis. Elife 5:
Falahati, Hanieh; Pelham-Webb, Bobbie; Blythe, Shelby et al. (2016) Nucleation by rRNA Dictates the Precision of Nucleolus Assembly. Curr Biol 26:277-85
Weng, Mo; Wieschaus, Eric (2016) Myosin-dependent remodeling of adherens junctions protects junctions from Snail-dependent disassembly. J Cell Biol 212:219-29
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 (2015) Zygotic genome activation triggers the DNA replication checkpoint at the midblastula transition. Cell 160:1169-81
He, Bing; Doubrovinski, Konstantin; Polyakov, Oleg et al. (2014) Apical constriction drives tissue-scale hydrodynamic flow to mediate cell elongation. Nature 508:392-6
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
Khan, Zia; Wang, Yu-Chiun; Wieschaus, Eric F et al. (2014) Quantitative 4D analyses of epithelial folding during Drosophila gastrulation. Development 141:2895-900
Di Talia, Stefano; Wieschaus, Eric F (2014) Simple biochemical pathways far from steady state can provide switchlike and integrated responses. Biophys J 107:L1-4
Di Talia, Stefano; She, Richard; Blythe, Shelby A et al. (2013) Posttranslational control of Cdc25 degradation terminates Drosophila's early cell-cycle program. Curr Biol 23:127-32

Showing the most recent 10 out of 54 publications