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 #
5R37HD015587-31
Application #
8466999
Study Section
Special Emphasis Panel (NSS)
Program Officer
Coulombe, James N
Project Start
1981-08-01
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
31
Fiscal Year
2013
Total Cost
$186,506
Indirect Cost
$67,881
Name
Princeton University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
He, Bing; Doubrovinski, Konstantin; Polyakov, Oleg et al. (2014) Apical constriction drives tissue-scale hydrodynamic flow to mediate cell elongation. Nature 508:392-6
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
Wang, Yu-Chiun; Khan, Zia; Wieschaus, Eric F (2013) Distinct Rap1 activity states control the extent of epithelial invagination via ?-catenin. Dev Cell 25:299-309
Wang, Yu-Chiun; Khan, Zia; Kaschube, Matthias et al. (2012) Differential positioning of adherens junctions is associated with initiation of epithelial folding. Nature 484:390-3
Lu, Xuemin; Drocco, Jeff; Wieschaus, Eric F (2010) Cell cycle regulation via inter-nuclear communication during the early embryonic development of Drosophila melanogaster. Cell Cycle 9:2908-10
Martin, Adam C; Gelbart, Michael; Fernandez-Gonzalez, Rodrigo et al. (2010) Integration of contractile forces during tissue invagination. J Cell Biol 188:735-49
Martin, Adam C; Kaschube, Matthias; Wieschaus, Eric F (2009) Pulsed contractions of an actin-myosin network drive apical constriction. Nature 457:495-9
Lu, Xuemin; Li, Jennifer M; Elemento, Olivier et al. (2009) Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition. Development 136:2101-10

Showing the most recent 10 out of 44 publications