The Berg Lab

Welcome to the Berg Lab

In the Berg Lab, we use the fruit fly Drosophila melanogaster to investigate cell communication and cell migration, two processes critical for development and human disease progression. We study the signaling pathways that pattern the follicular epithelium surrounding the oocyte. We also investigate the link between these cell fates and the subsequent cell shape changes and movements that reorganize the flat epithelium into two closed tubes. Patterning and morphogenesis are the fundamental building blocks of all developmental processes. Learn more about these processes and the scientists who study them by exploring our site.

People

The Berg laboratory welcomes all to our web site. Meet our group! Explore our work!

Celeste Berg

Celeste Berg

I have a twin sister and she looks more like my Dad. My parents always treated us exactly the same, yet we are so different! Not only do our physical features differ but our personalities and temperaments differ too. She was always the angel, doing kind things for others (the 'good' twin), and I was more critical (the 'bad' twin). From early on, I wondered why we were alike and yet not alike. Now I am a geneticist and I study how genes control our development and make us what we are.

Michael Boyle

Michael Boyle

Faith Hassinger

Faith Hassinger

Kevin Lam

Kevin Lam

Philip Louie

Philip Louie

Atriya Salamati

Atriya Salamati

Research

In the U.S., birth defects are the leading cause of death in children (National Vital Statistics Report 2004). A surprising 3% of all newborns exhibit major malformations; of these, one fifth clearly result from genetic disorders. By defining the mechanisms and molecules that control developmental processes , we can develop diagnostic tools for identifying risks factors and, in the long run, evaluate the efficacy of potential treatments.

What are the mechanisms and molecules that control development? Genetic and genomic studies reveal that developmental processes are similar in all animals. We are using Drosophila to investigate how flat epithelial sheets are patterned into distinct cell types and how these cell types change shape and rearrange to make a pair of simple tubes called dorsal appendages (Dorman et al. 2004; reviewed by Berg 2005). This process occurs in the follicle cell layer that surrounds the oocyte and is tied to establishing dorsal/ventral polarity in the embryo. In vertebrates, tube formation produces the heart, kidneys, lungs, gut, and neural tube; dorsal appendage formation resembles these more complex processes but is easier to study because it does not involve cell division or cell death. We also have sophisticated genetic tools for manipulating gene function, a culture system for imaging events live, and a battery of markers for following the fate and behavior of the cells.

We are interested in four broad questions:

How do genes control the differences in size and shape of the tubes?

Genetic variants exhibit striking differences in morphology that mimic natural shapes throughout the animal kingdom. Some variations affect patterning and alter the number of cells fated to produce the tubes; others affect morphogenesis and alter the cell biological processes that produce the tubes (Berg 2005). What are these genes and how similar are their roles in different developmental processes?

How does a gradient of signaling information resolve into a sharp boundary between two distinct cell types?

Several signaling pathways contribute to defining the two types of cells that make the dorsal appendage tubes. EGF and BMP signals are expressed in a graded fashion in the dorsal anterior follicle cells. These molecules induce Notch and Wingless signaling, which subdivide the primordium and establish a boundary between the two cell types (Ward and Berg 2005; Ward et al. 2006). How do these pathways refine the pattern within the epithelium?

How do the two cell types coordinate their efforts to produce a tube?

Cells expressing high levels of the transcription factor Broad constrict their apices and undergo convergent extension to form the roof and sides of the tube. Cells expressing the protease Rhomboid elongate dramatically and zipper together their apices to seal off the floor of the tube (Dorman et al. 2004). Subsequent shape changes and rearrangements produce the final form of the tube. How does each group of cells coordinate their activities, within each group and between the two cell types?

What other genes contribute to tube formation?

Although we know dozens of genes that affect the patterning and morphogenesis of the dorsal-appendage tubes, we have only just begun to understand this complex process. Classical genetic screens, transposon mutagenesis screens, mosaic analysis with a genome-wide deletion set, micro-array analysis to investigate transcript levels and chromatin differences, and RNA interference or drug studies using cultured egg chambers provide tools to identify new genes that regulate development.

Drosophila provides an outstanding system for investigating the fundamental processes that regulate development and for identifying the genes that, when mutated, contribute to birth defects.

Culture Protocol This section is a hyper link to here.

Movies

Using our culture protocol, we have analyzed the development of late stage egg chambers using Green Fluorescent Protein fused to the actin-binding protein Moesin (Bloor and Kiehart 2001) or to histone 2A (Clarkson and Saint 1999). These studies reveal the dynamic events of tube formation and elongation, and demonstrate that the epithelial sheet folds as a single layer into a tube. Fixed tissue stained for roof- and floor-cell markers compliments the live image analysis.

Potential Projects

Lab Meetings

Publications

Publications in refereed journals:

• Ward, E. J., Zhou, X., Riddiford, L., M., Berg, C. A., and Ruohola-Baker, H. 2006.
  Border of Notch activity establishes a boundary between the two dorsal-appendage-tube cell types.
  Developmental Biology 297: 461 - 470.

• Berg, C. A. 2005.
  The Drosophila shell game: Patterning genes and morphological change.
  Trends in Genetics 21: 346 - 355.

• Ward, E. J. and Berg, C. A. 2005.
  Juxtaposition between two cell types is necessary for dorsal appendage tube formation.
  Mechanisms of Development 122: 241 - 255.

• Dorman, J. B., James, K. E., Fraser, S. E., Kiehart, D. P., and Berg, C. A. 2004.
  bullwinkle is required for epithelial morphogenesis during Drosophila oogenesis.
  Developmental Biology 267: 320 - 341. Cover.
  

• Tran, D. H. and Berg, C.A. 2003.
  bullwinkle and shark regulate dorsal-appendage morphogenesis in Drosophila oogenesis.
  Development 130: 6273 - 6282.
  In This Issue! review

• James, K. E. and Berg, C. A. 2003.
  Temporal comparison of Broad-Complex expression during eggshell-appendage patterning and morphogenesis in two Drosophila species with different eggshell-appendage numbers.
  Gene Expression Patterns 3: 629 - 634.

• French, R. F., Cosand, K. A., and Berg, C. A. 2003.
  The Drosophila female sterile mutation twin peaks is a novel allele of tramtrack and reveals a requirement for TTK69 in regulating epithelial morphogenesis.
  Developmental Biology 253: 18 - 35.

• Kot, M., Silverman, E., and Berg, C. A. 2003.
  Zipf's law and the diversity of biology newsgroups.
  Scientometrics 56: 247 - 257.

• Ward, E. J., Thaipisuttikul, I., Terayama, M., French, R. L., Jackson, S. M., Cosand, K. A., Tobler, K. J., Dorman, J. B., and Berg, C. A. 2002.
  GAL4 expression patterns during Drosophila development.
  Genesis 34: 46 - 50.

• Jackson, S. M. and Berg, C. A. 2002.
  An A-kinase anchoring protein is required for PKA-RII membrane localization and ring canal morphology during oogenesis in Drosophila.
  Development 129: 4423 - 4433.

• James, K. E., Dorman, J. B., and Berg, C. A. 2002.
  Mosaic analyses reveal the function of Drosophila Ras in embryonic dorsoventral patterning and dorsal follicle cell morphogenesis.
  Development 129: 2209 - 2222. Cover.
  

• Volpe, A., Horowitz, H., Grafer, C. M., Jackson, S. M., and Berg, C. A. 2001.
  Drosophila rhino encodes a female-specific chromo-domain protein that affects chromosome structure and egg polarity.
  Genetics 159: 1117 - 1134.

• Schnorr, J. D., Holdcraft, R., Chevalier, B., and Berg, C. A. 2001.
  Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.
  Genetics 159: 609 - 622.

• D'Argenio, D., Gallagher, L. A., Berg, C. A., and Manoil, C. 2001.
  Drosophila as a model host for Pseudomonas aeruginosa infection.
  Journal of Bacteriology 183: 1466 - 1471.

• Jackson, S. M. and Berg, C. A. 1999.
  Soma-to-germline interactions during Drosophila oogenesis are influenced by dose-sensitive interactions between cut and the genes cappuccino, ovarian tumor and agnostic.
  Genetics 153: 289 - 303.

• Webster, P., Liang, L., Berg, C. A., Lasko, P., and Macdonald, P. 1997.
  Translational repressor Bruno plays multiple roles in development and is widely conserved.
  Genes & Development 11: 2510 - 2521.

• Schnorr, J. D. and Berg, C. A. 1996.
  Differential activity of Ras1 during patterning of the Drosophila dorsoventral axis.
  Genetics 144: 1545 - 1557.
  Horowitz, H. and Berg, C. A. 1996.
  The Drosophila pipsqueak gene encodes a nuclear BTB-domain-containing protein required early in oogenesis.
  Development 122: 1859 - 1871.

• Gillespie, D. and Berg, C. A. 1995.
  homeless is required for RNA localization in Drosophila oogenesis and encodes a new member of the DE-H family of RNA-dependent ATPases.
  Genes & Development 9: 2495 - 2508. Cover.
  

• Rittenhouse, K. R. and Berg, C. A. 1995.
  Mutations in the Drosophila gene bullwinkle cause the formation of abnormal eggshell structures and bicaudal embryos.
  Development 121: 3023 - 3033.

• Horowitz, H. and Berg, C. A. 1995.
  Aberrant splicing and transcription termination caused by P element insertion into the intron of a Drosophila gene.
  Genetics 139: 327 - 335.

• Berg, C. A. and Spradling, A. C. 1991.
  Studies on the rate and site-specificity of P-element transposition.
  Genetics 127: 515 - 524.
  Cooley, L., Berg, C. A., and Spradling, A. C. 1988.
  Controlling P-element insertional mutagenesis.
  Trends in Genetics 4: 254 - 258. Cover.
  

• Steitz, J. A., Berg, C. A., Hendrick, J. P., La Branche-Chabot, H., Metspalu, A., Rinke, J., and Yario, T. 1988.
  A 5S rRNA/L5 complex is a precursor to ribosome assembly in mammalian cells.
  Journal of Cell Biology 106: 545 - 556.

• Callan, H. C., Gall, J. G., and Berg, C. A. 1987.
  The lampbrush chromosomes of Xenopus laevis: Preparation, identification, and distribution of 5S DNA sequences.
  Chromosoma 95: 236 - 250.

• Berg, C. A. and Gall, J. G. 1986.
  Microinjected Tetrahymena rDNA ends are not recognized as telomeres in Xenopus eggs.
  Journal of Cell Biology 103: 691 - 698.

Book chapters:

• Cooley, L., Berg, C. A., Kelley., R., McKearin, D., and Spradling, A. C. 1988.
  Identifying and cloning Drosophila genes by single P-element insertional mutagenesis.
  In: Progress in Nucleic Acid Research and Molecular Biology: Transposable Elements in Mutagenesis and Gene Expression.
  vol. 36 (Cohn, W. ed.) Academic Press, Orlando, Florida. pp. 99 - 109.

• Steitz, J. A., Berg, C. A., Gottlieb, E., Hardin, J. A., Hashimoto, C., Hendrick, J. P., Hinterberger, M., Krikeles, M., Lerner, M. R., Mount, S. M., Pettersson, I., Rinke, J., Rosa, M. D., and Wolin, S. L. 1982.
  Structure and function of small ribonucleoproteins from eukaryotic cells.
  In: International Symposium Princess Takamatsu Cancer Research Fund, Adp-Ribosy
  vol. 12 (Miwa, M. ed.) Brill Academic Publishers, Leiden, The Netherlands. pp. 101 - 107.

Published videos:

• Our studies on tube formation during development involve time-lapse imaging using the confocal microscope to examine cell shape changes and movements. Movies illustrating various events during this tube-forming process, published by Elsevier press, are also accessible at Movies.

Manuscripts:

• Berg, C. A., Terayama, M., Tran, D. H., Rittenhouse, K. L., French, R. L., Wu, T., and Trent, C.
  The SOX92D locus regulates patterning and morphogenesis in Drosophila.
  Manuscript in preparation.

Teaching

I have taught a variety of undergraduate and graduate courses at the University of Washington. These courses include:

GENOME 371 This section is a hyper link to here.

GENOME 553 This section is a hyper link to here.

Outreach

Contact Information