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Eric Wieschaus

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

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: 2101-2110. PubMed

Martin AC, Kaschube M, Wieschaus EF. (2009) Pulsed contractions of an actin-myosin network drive apical constriction. Nature 457: 495-499. PubMed

Sokac AM, Wieschaus E. (2008) Zygotically controlled F-actin establishes cortical compartments to stabilize furrows during Drosophila cellularization. J Cell Sci. 121: 1815-1824. PubMed

Sokac AM, Wieschaus E. (2008) Local actin-dependent endocytosis is zygotically controlled to initiate Drosophila cellularization. Dev Cell. 14: 775-786. 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: 350-358. 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: 153-164. PubMed

Gregor T, Wieschaus EF, McGregor AP, Bialek W, Tank DW (2007). Stability and nuclear dynamics of the bicoid morphogen gradient. Cell 130: 141-152. 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: 509-512. PubMed

De Renzis S, Yu J, Zinzen R and Wieschaus E (2006). Dorsal-ventral pattern of delta trafficking is established by a snail-tom-neuralized pathway. Dev Cell 10: 257-264. 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 USA 102: 18403-18407. PubMed

Goodliffe JM, Wieschaus E and Cole MD (2005). Polycomb mediates Myc autorepression and its transcriptional control of many loci in Drosophila. Genes Dev 19: 2941-2946. PubMed

Houchmandzadeh B, Wieschaus E and 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, Phelps CB, Brand AH, Wieschaus EF (2005). folded gastrulation, cell shape change and the control of myosin localization. Development 132: 4165-4178. PubMed

Zallen JA and Wieschaus E (2004). Patterned gene expression directs bipolar planar polarity in Drosophila. Dev Cell 6: 343-355. PubMed

Tolwinski NS and Wieschaus E (2004). A nuclear escort for beta-catenin. Nat Cell Biol 6: 579-580. PubMed

Tolwinski NS and Wieschaus E (2004). Rethinking WNT signaling. Trends Genet 20: 177-181. PubMed

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

Thomas JH and Wieschaus E (2004). src64 and tec29 are required for microfilament contraction during Drosophila cellularization. Development 131: 863-871. 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: 407-418. PubMed

Grosshans J, Muller HA and Wieschaus E (2003). Control of cleavage cycles in Drosophila embryos by fruhstart. Dev Cell 5: 285-294. PubMed

Dawes-Hoang RE, Zallen JA and 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 and Wieschaus E (2002). Junctions as organizing centers in epithelial cells? A fly perspective. Traffic 3: 92-97. PubMed

Lecuit T, Samanta R and Wieschaus E (2002). slam encodes a developmental regulator of polarized membrane growth during cleavage of the Drosophila embryo. Dev Cell 2: 425-436. PubMed

Hunter C, Sung P, Schejter ED and Wieschaus E (2002). Conserved domains of the Nullo protein required for cell-surface localization and formation of adherens junctions. Mol Biol Cell 13: 146-157. PubMed

Houchmandzadeh B, Wieschaus E and 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 and Wieschaus EF (2002). Coordination of opposite-polarity microtubule motors. J Cell Biol 156: 715-724. PubMed

Ahmed Y, Nouri A and Wieschaus E (2002). Drosophila Apc1 and Apc2 regulate Wingless transduction throughout development. Development 129: 1751-1762. PubMed

Tolwinski NS and Wieschaus E (2001). Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan. Development 128: 2107-2117. PubMed

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

Blankenship JT and Wieschaus E (2001). Two new roles for the Drosophila AP patterning system in early morphogenesis. Development 128: 5129-5138. 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 and Wieschaus E (2000). Polarized insertion of new membrane from a cytoplasmic reservoir during cleavage of the Drosophila embryo. J Cell Biol 150: 849-860. PubMed

Hunter C and 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 and Wieschaus E (2000). A genetic link between morphogenesis and cell division during formation of the ventral furrow in Drosophila. Cell 101: 523-531. PubMed

Gross SP, Welte MA, Block SM and Wieschaus EF (2000). Dynein-mediated cargo transport in vivo. A switch controls travel distance. J Cell Biol 148: 945-956. PubMed

Muller H, Samanta R and Wieschaus E (1999). Wingless signaling in the Drosophila embryo: zygotic requirements and the role of the frizzled genes. Development 126: 577-586. PubMed

Jazwinska A, Kirov N, Wieschaus E, Roth S and Rushlow C (1999). The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation. Cell 96: 563-573. PubMed

Welte MA, Gross SP, Postner M, Block SM and Wieschaus EF (1998). Developmental regulation of vesicle transport in Drosophila embryos: forces and kinetics. Cell 92: 547-557. PubMed

Schupbach T and Wieschaus E (1998). Probing for gene specificity in epithelial development. Int J Dev Biol 42: 249-255. PubMed

Morize P, Christiansen AE, Costa M, Parks S and Wieschaus E (1998). Hyperactivation of the folded gastrulation pathway induces specific cell shape changes. Development 125: 589-597. PubMed

Ahmed Y, Hayashi S, Levine A and Wieschaus E (1998). Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal development. Cell 93: 1171-1182. PubMed