Faculty & Research
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Molecular Biology Faculty

Eric F. Wieschaus

Squibb Professor in Molecular Biology
Professor of Molecular Biology
and the Lewis-Sigler Institute for Integrative Genomics
NOBEL PRIZE WINNER (1995)

Eric Weischaus

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Phone (609) 258-5383
locationMoffet Lab, 435
Phone Lab (609) 258-5401
Faculty Assistant
Carolynne Lewis-Arévalo
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Phone (609) 258-2933

 

Research Focus

Embryonic development of Drosophila melanogaster

We are interested in the patterning that occurs in the early Drosophila embryo. Most of the gene products used by the embryo at these stages are already present in the unfertilized egg and were produced by maternal transcription during oogenesis. A small number of gene products, however, are supplied by transcription in the embryo itself. We have focused on these "zygotically" active genes because we believe the temporal and spatial pattern of their transcription may provide the triggers controlling the normal sequence of embryonic development.

The earliest requirements for zygotic gene activity become apparent at cellularization. The early cleavage divisions in Drosophila involve nuclear mitoses without intervening cytokinesis. Ultimately, they produce a syncytial blastoderm of 6,000 nuclei. "Cellularization" of these nuclei requires a massive, rapid reorganization of the embryonic cytoskeleton that occurs after the 13th cleavage cycle. This reorganization is blocked by inhibitors of RNA synthesis such as a-amanitin. By screening a collection of chromosomal deletions that span the entire Drosophila genome, we identified those zygotically active loci required at different stages during cellularization. In embryos deficient for three of these genes, the hexagonal arrays of F-actin required to pull plasma membrane down between adjacent nuclei are abnormal, and multiple nuclei are enclosed into single cells. Other loci affect cytoplasmic clearing, membrane synthesis, and the morphology of contractile rings. We have cloned several of these genes and have characterized their role in restructuring the embryonic cytoskeleton. We have also begun analysis of the role of microtubule- based transport in the early embryo, using optical traps and image enhancement to measure forces and kinetic behaviors of individual cellular organelles. Once the embryo has completed cellularization, it begins gastrulation. A ventral furrow and posterior midgut are formed by characteristic changes in cell shape that occur only in the ventral and posterior regions of the embryo. Our analysis has concentrated on genes (folded gastrulation [=fog] and concertina [= cta]) that are required for the process. Using genetic mosaics, we have shown that fog+ expression is required zygotically and only in specific regions of the embryo. Cta expression is required in the maternal germ line, and its RNA is uniform throughout the egg. The surprising homology of the cta gene product to G protein a-subunit argues for cell signaling process coordinating cell shape changes in each invagination.

We are also interested in how complex patterns of cell differentiation are established within epithelial cells at later stage of development. In Drosophila, maintenance of segmental pattern requires interactions between groups of cells that express different "segment polarity" genes. Our work has shown that changes in Armadillo protein levels are among the earliest responses to the intracellular signals that control patterning. Armadillo encodes the Drosophila homologue of §-catinin, a major component of vertebrate adhesive junctions. The proteins that regulate its expression in Drosophila are homologues of vertebrate proteins (Wnt-1, APC) that have been implicated in many forms of human cancer. We are using a variety of molecular and genetic strategies in Drosophila to determine how these genes interact with Armadillo to produce changes in cell morphology and behavior.


Selected Publications

Khan Z, Wang YC, Wieschaus EF, Kaschube M. (2014) Quantitative 4D analyses of epithelial folding during Drosophila gastrulation. Development. Jun 19. [Epub ahead of print]

He B, Doubrovinski K, Polyakov O, Wieschaus E. (2014) Apical constriction drives tissue-scale hydrodynamic flow to mediate cell elongation. Nature. 508: 392-96. Pubmed

Dubuis JO, Tkacik G, Wieschaus EF, Gregor T, Bialek W. (2013) Positional information, in bits. Proc Natl Acad Sci. 110: 16301-08. Pubmed

Wang YC, Khan Z, Wieschaus EF. (2013) Distinct Rap1 activity states control the extent of epithelial invagination via α-catenin. Dev Cell. 25: 299-309. Pubmed

Osterfield M, Du X, Schüpbach T, Wieschaus E, Shvartsman SY. (2013) Three-dimensional epithelial morphogenesis in the developing Drosophila egg. Dev Cell. 24: 400-10. Pubmed

Di Talia S, She R, Blythe SA, Lu X, Zhang QF, Wieschaus EF. (2013) Posttranslational control of Cdc25 degradation terminates Drosophila's early cell-cycle program. Curr Biol. 23: 127-32. Pubmed

Gelbart MA, He B, Martin AC, Thiberge SY, Wieschaus EF, Kaschube M. (2012) Volume conservation principle involved in cell lengthening and nucleus movement during tissue morphogenesis. Proc Natl Acad Sci. 109: 19298-303. Pubmed

Grimm O, Zini VS, Kim Y, Casanova J, Shvartsman SY, Wieschaus E. (2012) Torso RTK controls Capicua degradation by changing its subcellular localization. Development. 139: 3962-68. Pubmed

Drocco JA, Wieschaus EF, Tank DW. (2012) The synthesis-diffusion-degradation model explains Bicoid gradient formation in unfertilized eggs. Phys Biol.  9: 055004. Pubmed

He B, Caudy A, Parsons L,...Wieschaus E. (2012) Mapping the pericentric heterochromatin by comparative genomic hybridization analysis and chromosome deletions in Drosophila melanogaster. Genome Res. 22: 2507-19. Pubmed

Di Talia S, Wieschaus EF. (2012) Short-term integration of Cdc25 dynamics controls mitotic entry during Drosophila gastrulation. Dev Cell. 22: 763-74. PubMed

Wang YC, Khan Z, Kaschube M, Wieschaus EF. (2012) Differential positioning of adherens junctions is associated with initiation of epithelial folding. Nature. 484: 390-93. PubMed

Drocco JA, Grimm O, Tank DW, Wieschaus E. (2011) Measurement and perturbation of morphogen lifetime: effects on gradient shape. Biophys J. 101: 1807-15. PubMed

Little SC, Wieschaus EF. (2011) Shifting patterns: merging molecules, morphogens, motility, and methodology. Dev Cell. 21: 2-4. PubMed

Little SC, Tkačik G, Kneeland TB, Wieschaus EF, Gregor T. (2011) The formation of the bicoid morphogen gradient requires protein movement from anteriorly localized mRNA. PLoS Biol. 9: e1000596. PubMed

Lu X, Drocco J, Wieschaus EF. (2010) Cell cycle regulation via inter-nuclear communication during the early embryonic development of Drosophila melanogaster. Cell Cycle. 9: 2908-10. PubMed

Grimm O, Coppey M, Wieschaus E. (2010) Modelling the Bicoid gradient. Development. 137: 2253-64. PubMed

Martin AC, Gelbart M, Fernandez-Gonzalez R, Kaschube M, Wieschaus EF. (2010) Integration of contractile forces during tissue invagination. J Cell Biol. 188: 735-49. PubMed

Lu X, Li JM, Elemento O, Tavazoie S, Wieschaus EF. (2009) Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition. Development. 136: 2101-10. PubMed

Martin AC, Kaschube M, Wieschaus EF. (2009) Pulsed contractions of an actin-myosin network drive apical constriction. Nature. 457: 495-99. PubMed

Sokac AM, Wieschaus E. (2008) Zygotically controlled F-actin establishes cortical compartments to stabilize furrows during Drosophila cellularization. J Cell Sci. 121: 1815-24. PubMed

Sokac AM, Wieschaus E. (2008) Local actin-dependent endocytosis is zygotically controlled to initiate Drosophila cellularization. Dev Cell. 14: 775-86. PubMed

Gregor T, McGregor AP, Wieschaus EF. (2008) Shape and function of the Bicoid morphogen gradient in dipteran species with different sized embryos. Dev Biol. 316: 350-58. PubMed

Bialek W, Gregor T, Tank DW, Wieschaus EF. (2008) Response: can we fit all of the data? Cell. 132: 17-18. PubMed

Gregor T, Tank DW, Wieschaus EF, Bialek W. (2007) Probing the limits to positional information. Cell. 130: 153-64. PubMed

Gregor T, Wieschaus EF, McGregor AP, Bialek W, Tank DW (2007). Stability and nuclear dynamics of the bicoid morphogen gradient. Cell. 130: 141-52. PubMed

De Renzis S, Elemento O, Tavazoie S, Wieschaus EF. (2007) Unmasking activation of the zygotic genome using chromosomal deletions in the Drosophila embryo. PLoS Biol. 5: e117. (Erratum in: PLoS Biol 5: e213, PLoS Biol 5: e195.) PubMed

Goodliffe JM, Cole MD, Wieschaus E. (2007) Coordinated regulation of Myc trans-activation targets by Polycomb and the Trithorax group protein Ash1. BMC Mol Biol. 8: 40. PubMed

Frydman HM, Li JM, Robson DN, Wieschaus E. (2006) Somatic stem cell niche tropism in Wolbachia. Nature. 441: 509-12. PubMed

De Renzis S, Yu J, Zinzen R, Wieschaus E. (2006) Dorsal-ventral pattern of delta trafficking is established by a snail-tom-neuralized pathway. Dev Cell. 10: 257-64. PubMed

Gregor T, Bialek W, de Ruyter van Steveninck RR, Tank DW, Wieschaus EF. (2005) Diffusion and scaling during early embryonic pattern formation. Proc Natl Acad Sci. 102: 18403-07. PubMed

Goodliffe JM, Wieschaus E, Cole MD. (2005) Polycomb mediates Myc autorepression and its transcriptional control of many loci in Drosophila. Genes Dev. 19: 2941-46. PubMed

Houchmandzadeh B, Wieschaus E, Leibler S. (2005) Precise domain specification in the developing Drosophila embryo. Phys Rev E Stat Nonlin Soft Matter Phys. 72: 061920. PubMed

Ferree PM, Frydman HM, Li JM, Cao J, Wieschaus E, Sullivan W. (2005) Wolbachia utilizes host microtubules and Dynein for anterior localization in the Drosophila oocyte. PLoS Pathog. 1: e14. PubMed

Dawes-Hoang RE, Parmar KM, Christiansen AE,...Wieschaus EF. (2005) folded gastrulation, cell shape change and the control of myosin localization. Development. 132: 4165-78. PubMed

Zallen JA and Wieschaus E. (2004) Patterned gene expression directs bipolar planar polarity in Drosophila. Dev Cell 6: 343-55. PubMed

Tolwinski NS, Wieschaus E. (2004) A nuclear escort for beta-catenin. Nat Cell Biol. 6: 579-80. PubMed

Tolwinski NS, Wieschaus E. (2004) Rethinking WNT signaling. Trends Genet. 20: 177-81. PubMed

Tolwinski NS, Wieschaus E. (2004) A nuclear function for armadillo/beta-catenin. PLoS Biol. 2: E95. PubMed

Thomas JH, Wieschaus E. (2004) src64 and tec29 are required for microfilament contraction during Drosophila cellularization. Development. 131: 863-71. PubMed

Tolwinski NS, Wehrli M, Rives A, Erdeniz N, DiNardo S, Wieschaus E. (2003) Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity. Dev Cell. 4: 407-18. PubMed

Grosshans J, Muller HA, Wieschaus E. (2003) Control of cleavage cycles in Drosophila embryos by fruhstart. Dev Cell. 5: 285-94. PubMed

Dawes-Hoang RE, Zallen JA, Wieschaus EF. (2003). Bringing classical embryology to C elegans gastrulation. Dev Cell. 4: 6-8. PubMed

Zallen JA, Cohen Y, Hudson AM, Cooley L, Wieschaus E, Schejter ED. (2002) SCAR is a primary regulator of Arp2/3-dependent morphological events in Drosophila. J Cell Biol. 156: 689-701. PubMed

Lecuit T, Wieschaus E. (2002) Junctions as organizing centers in epithelial cells? A fly perspective. Traffic. 3: 92-97. PubMed

Lecuit T, Samanta R, Wieschaus E. (2002) slam encodes a developmental regulator of polarized membrane growth during cleavage of the Drosophila embryo. Dev Cell. 2: 425-36. PubMed

Hunter C, Sung P, Schejter ED, Wieschaus E. (2002) Conserved domains of the Nullo protein required for cell-surface localization and formation of adherens junctions. Mol Biol Cell. 13: 146-57. PubMed

Houchmandzadeh B, Wieschaus E, Leibler S. (2002) Establishment of developmental precision and proportions in the early Drosophila embryo. Nature. 415: 798-802. PubMed

Gross SP, Welte MA, Block SM, Wieschaus EF. (2002) Coordination of opposite-polarity microtubule motors. J Cell Biol. 156: 715-24. PubMed

Ahmed Y, Nouri A, Wieschaus E. (2002) Drosophila Apc1 and Apc2 regulate Wingless transduction throughout development. Development. 129: 1751-62. PubMed

Tolwinski NS, Wieschaus E. (2001) Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan. Development. 128: 2107-17. PubMed

Dawes-Hoang RE, Wieschaus EF. (2001) Cell and developmental biology--a shared past, an intertwined future. Dev Cell. 1: 27-36. PubMed

Blankenship JT, Wieschaus E. (2001) Two new roles for the Drosophila AP patterning system in early morphogenesis. Development. 128: 5129-38. PubMed

Arrow KJ, Axelrod J, Benacerraf B, Berg P, Bishop JM, et al. (2001). Nobel laureates' letter to President Bush. Washington Post A02.

Lecuit T, Wieschaus E. (2000) Polarized insertion of new membrane from a cytoplasmic reservoir during cleavage of the Drosophila embryo. J Cell Biol. 150: 849-60. PubMed

Hunter C, Wieschaus E. (2000) Regulated expression of nullo is required for the formation of distinct apical and basal adherens junctions in the Drosophila blastoderm. J Cell Biol. 150: 391-401. PubMed

Grosshans J, Wieschaus E. (2000) A genetic link between morphogenesis and cell division during formation of the ventral furrow in Drosophila. Cell. 101: 523-31. PubMed

Gross SP, Welte MA, Block SM, Wieschaus EF. (2000) Dynein-mediated cargo transport in vivo. A switch controls travel distance. J Cell Biol. 148: 945-56. PubMed

Muller H, Samanta R, Wieschaus E. (1999) Wingless signaling in the Drosophila embryo: zygotic requirements and the role of the frizzled genes. Development. 126: 577-86. PubMed

Jazwinska A, Kirov N, Wieschaus E, Roth S, Rushlow C. (1999) The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation. Cell. 96: 563-73. PubMed

Welte MA, Gross SP, Postner M, Block SM, Wieschaus EF. (1998) Developmental regulation of vesicle transport in Drosophila embryos: forces and kinetics. Cell. 92: 547-57. PubMed

Schupbach T, Wieschaus E. (1998) Probing for gene specificity in epithelial development. Int J Dev Biol. 42: 249-55. PubMed

Morize P, Christiansen AE, Costa M, Parks S, Wieschaus E. (1998) Hyperactivation of the folded gastrulation pathway induces specific cell shape changes. Development. 125: 589-97. PubMed

Ahmed Y, Hayashi S, Levine A, Wieschaus E. (1998) Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal development. Cell. 93: 1171-82. PubMed

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