Our long-term objective is to understand the complex network of genetic interactions that control gene expression underlying the processes of normal development, disease and evolution. At the Berkeley Drosophila Genome Project (BDGP), we have established a gene expression resource for Drosophila development that contains spatial and temporal embryonic expression patterns, annotations of the patterns using a standardized, controlled vocabulary, based on an anatomical ontology and a standardized virtual representation of the patterns. We created tools to identify similar, partially overlapping or anti-correlated expression. Our database currently contains over 100,000 annotated images showing expression patterns generated using in-situ hybridization of staged whole-mounted embryos for approximately 60% (8500) of the protein-coding genes in the Drosophila genome. We propose to: (1) obtain expression patterns for as many of the remaining 40% of the protein-coding genes as possible, (2) develop fully automatic image acquisition with a motorized microscope and analysis pipeline to accelerate data collection and in preparation for high-throughput studies, (3) continue advancements and refinements to our virtual image representation and create web-tools and interfaces for the research community to conduct analysis with our dataset and uploaded images and (4) characterize and analyze expression patterns of conserved regulatory modules from transcription factors. The primary resource for generation of RNA probes is our Drosophila Gene Collection (DGC), which currently contains cDNA clones corresponding to 88% of the annotated genes. To capture expression patterns for genes that do not have a representative cDNA clone (12%), we used gene-specific PCR products to generate RNA probes in 96- well format. The gene expression data produced by our study will provide fundamental information for elaborating the function of the 13,831 protein-coding genes in Drosophila and will aid in elucidating the function of the homologous genes in other eukaryotes, including humans. Genome wide association studies have shown fundamental roles for regulatory regions and gene expression in human diseases. The functional analysis of regulatory regions will provide novel insights into the developmental roles of transcription factors. In addition, the integration of the gene expression data with regulatory and gene sequences will promote research to discover networks of regulatory interactions.

Public Health Relevance

Elucidating the mechanisms responsible for genome-wide gene expression and regulation in Drosophila development will aid in understanding normal growth and differentiation of tissues in humans, prerequisites for understanding human disease.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Hoodbhoy, Tanya
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Lawrence Berkeley National Laboratory
Organized Research Units
United States
Zip Code
Brown, James B; Boley, Nathan; Eisman, Robert et al. (2014) Diversity and dynamics of the Drosophila transcriptome. Nature 512:393-9
Gerstein, Mark B; Rozowsky, Joel; Yan, Koon-Kiu et al. (2014) Comparative analysis of the transcriptome across distant species. Nature 512:445-8
Thomas, Sean; Li, Xiao-Yong; Sabo, Peter J et al. (2011) Dynamic reprogramming of chromatin accessibility during Drosophila embryo development. Genome Biol 12:R43
Frise, Erwin; Hammonds, Ann S; Celniker, Susan E (2010) Systematic image-driven analysis of the spatial Drosophila embryonic expression landscape. Mol Syst Biol 6:345
Weiszmann, Richard; Hammonds, Ann S; Celniker, Susan E (2009) Determination of gene expression patterns using high-throughput RNA in situ hybridization to whole-mount Drosophila embryos. Nat Protoc 4:605-18
Li, Xiao-yong; MacArthur, Stewart; Bourgon, Richard et al. (2008) Transcription factors bind thousands of active and inactive regions in the Drosophila blastoderm. PLoS Biol 6:e27
Pfeiffer, Barret D; Jenett, Arnim; Hammonds, Ann S et al. (2008) Tools for neuroanatomy and neurogenetics in Drosophila. Proc Natl Acad Sci U S A 105:9715-20
Tomancak, Pavel; Berman, Benjamin P; Beaton, Amy et al. (2007) Global analysis of patterns of gene expression during Drosophila embryogenesis. Genome Biol 8:R145