Patterns of gene expression in animal development

How genomic information determines the formation of an organism is a major challenge of biology in the post-genomic era. The restriction of gene activity to subsets of cells during development leads to morphological and physiological specialization allowing the formation of tissues and organs. Although many mechanisms play a role, regulation of transcription is a primary cause of tissue specific gene expression. Our understanding paints a picture of transcriptional regulation as a complex interplay of cis-regulatory sequence elements interacting with trans-acting proteins. Combining an understanding of transcriptional regulation together with a complete genome sequence may ultimately allow a description of a developing organism as a network of interacting genetic and protein components. However, before we can begin to attempt to decipher the developmental puzzle it is essential to assemble spatio-temporal gene expression data on genome-wide scale.

It is arguable that the knowledge of the precise spatial and temporal specificity of gene expression is the necessary prerequisite for understanding gene function in animal development. The availability of complete genome sequences allows us to determine patterns of gene expression systematically for all genes in the genome using the universal RNA in situ hybridization technique. We focus on the complex, well-understood and technically accessible process of Drosophila embryogenesis and aim to create the first complete atlas of spatio-temporal expression patterns in development. The process of capturing spatial gene expression data on a genome-wide scale requires combination of seemingly unrelated disciplines of embryology and bioinformatics. Currently the patterns of gene expression are documented by digital microscopy images of whole mount embryos stained with RNA probes specific for individual genes. The images are annotated with controlled vocabularies that represent our current knowledge of the embryo anatomy. The dataset of more then 75,000 annotated embryo images representing about 50% of Drosophila genes provides solid observational foundation for the analysis of the relationship between the genome sequence, tissue specific gene expression and animal development (www.fruitfly.org/cgi-bin/ex/insitu.pl).

: Sampling of patterns of gene expression in Drosophila embryogenesis.

The complete atlas of patterns of gene expression will ultimately contain data for all transcripts generated from the Drosophila genome. We are expanding the scope of the project to include individual alternative transcripts, computational and micro-array based gene predictions and non-coding RNA genes. We also initiated parallel screens to determine gene expression patterns in other developmentally active Drosophila tissues such as imaginal discs and ovaries. In order to increase the resolution of pattern determination we employ multiplex high-throughput fluorescent RNA in situ to visualize precise overlap of expression domains of genes with related expression patterns. In the future we intend to gradually move from expert assisted capturing of tissue specificity in fixed embryos towards automated recording of the expression patterns in four-dimensions on live specimens. As a first step towards this goal we will establish a 3D model of the Drosophila embryo using the tissue specific markers identified in the course of this work.

We are also interested in studying the evolution of gene expression regulation in Drosophilids and on macro-evolutionary scale. Systematic survey of gene expression patterns of orthologous genes in closely related species of Drosophila revealed relatively high occurrence of significant differences in developmental gene expression. By combining the powerful Drosophila experimental toolkit with comparative sequence analysis we can identify sequence determinants of the observed expression changes and explain their evolutionary origin. These efforts are greatly facilitated by the recently established draft genome sequences of 12 species of Drosophila. Finally, image based gene expression resources similar to ours are generated for many other developmental model systems. The emerging challenge is to integrate these diverse datasets into a centralized database that will allow comprehensive studies of the roles of gene expression regulation in animal development across the tree of life.

Selected Publications

Langer C.C.H., Ejsmont R.K., Schönbauer C., Schnorrer F., Tomancak P., (2010) In Vivo RNAi Rescue in Drosophila melanogaster with Genomic Transgenes from Drosophila pseudoobscura. PLoS ONE 5(1): e8928. doi:10.1371/journal.pone.0008928

Ejsmont R., Sarov M., Winkler S., Lipinski K., Tomancak P. (2009)
A toolkit for high-throughput, cross-species gene engineering in Drosophila. Nature Methods 6, 435 - 437

Saalfeld S., Cardona A., Hartenstein V., Tomancak P. (2009)
CATMAID: Collaborative Annotation Toolkit for Massive Amounts of Image Data. Bioinformatics Apr 17. [Epub ahead of print]

Preibisch S., Saalfeld S., Tomancak P. (2009)
Globally optimal stitching of tiled 3D microscopic image acquisitions. Bioinformatics Jun 1;25(11):1463-5.

Lécuyer E., Yoshida H., Parthasarathy N., Alm C., Babak T., Cerovina T., Hughes T.R., Tomancak P., Krause H.M. (2007)
Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell Oct 5;131(1):174-87.

Tomancak P., Berman B.P., Beaton A., Weiszmann R., Kwan E., Hartenstein V., Celniker S.E., Rubin G.M. (2007)
Global analysis of patterns of gene expression during Drosophila embryogenesis. Genome Biol. 8(7):R145.

Aboobaker A.A., Tomancak P., Patel N., Rubin G.M., Lai E.C. (2005)
Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development.
Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18017-22

Lai E. C., Tomancak P., Williams R.W., Rubin G. M. (2003)
Computational identification of Drosophila microRNA genes.
Genome Biol. 4(7):R42

Tomancak P., Beaton A., Weiszmann R., Kwan E., Shu S., Lewis S. E., Richards S., Ashburner M., Hartenstein V., Celniker S. E., Rubin G. M. (2002)
Systematic determination of patterns of gene expression during Drosophila embryogenesis.
Genome Biol. 3(12):R88

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Pavel Tomancak research focus group leader contact publications Patterns of gene expression in animal development How genomic information determines the formation of an organism is a major challenge of biology in the post-genomic era. The restriction of gene activity to subsets of cells during development leads to morphological and physiological specialization allowing the formation of tissues and organs. Although many mechanisms play a role, regulation of transcription is a primary cause of tissue specific gene expression. Our understanding paints a picture of transcriptional regulation as a complex interplay of cis-regulatory sequence elements interacting with trans-acting proteins. Combining an understanding of transcriptional regulation together with a complete genome sequence may ultimately allow a description of a developing organism as a network of interacting genetic and protein components. However, before we can begin to attempt to decipher the developmental puzzle it is essential to assemble spatio-temporal gene expression data on genome-wide scale. It is arguable that the knowledge of the precise spatial and temporal specificity of gene expression is the necessary prerequisite for understanding gene function in animal development. The availability of complete genome sequences allows us to determine patterns of gene expression systematically for all genes in the genome using the universal RNA in situ hybridization technique. We focus on the complex, well-understood and technically accessible process of Drosophila embryogenesis and aim to create the first complete atlas of spatio-temporal expression patterns in development. The process of capturing spatial gene expression data on a genome-wide scale requires combination of seemingly unrelated disciplines of embryology and bioinformatics. Currently the patterns of gene expression are documented by digital microscopy images of whole mount embryos stained with RNA probes specific for individual genes. The images are annotated with controlled vocabularies that represent our current knowledge of the embryo anatomy. The dataset of more then 75,000 annotated embryo images representing about 50% of Drosophila genes provides solid observational foundation for the analysis of the relationship between the genome sequence, tissue specific gene expression and animal development (www.fruitfly.org/cgi-bin/ex/insitu.pl). Sampling of patterns of gene expression in Drosophila embryogenesis. The complete atlas of patterns of gene expression will ultimately contain data for all transcripts generated from the Drosophila genome. We are expanding the scope of the project to include individual alternative transcripts, computational and micro-array based gene predictions and non-coding RNA genes. We also initiated parallel screens to determine gene expression patterns in other developmentally active Drosophila tissues such as imaginal discs and ovaries. In order to increase the resolution of pattern determination we employ multiplex high-throughput fluorescent RNA in situ to visualize precise overlap of expression domains of genes with related expression patterns. In the future we intend to gradually move from expert assisted capturing of tissue specificity in fixed embryos towards automated recording of the expression patterns in four-dimensions on live specimens. As a first step towards this goal we will establish a 3D model of the Drosophila embryo using the tissue specific markers identified in the course of this work. We are also interested in studying the evolution of gene expression regulation in Drosophilids and on macro-evolutionary scale. Systematic survey of gene expression patterns of orthologous genes in closely related species of Drosophila revealed relatively high occurrence of significant differences in developmental gene expression. By combining the powerful Drosophila experimental toolkit with comparative sequence analysis we can identify sequence determinants of the observed expression changes and explain their evolutionary origin. These efforts are greatly facilitated by the recently established draft genome sequences of 12 species of Drosophila. Finally, image based gene expression resources similar to ours are generated for many other developmental model systems. The emerging challenge is to integrate these diverse datasets into a centralized database that will allow comprehensive studies of the roles of gene expression regulation in animal development across the tree of life. Selected Publications Langer C.C.H., Ejsmont R.K., Schönbauer C., Schnorrer F., Tomancak P., (2010) In Vivo RNAi Rescue in Drosophila melanogaster with Genomic Transgenes from Drosophila pseudoobscura. PLoS ONE 5(1): e8928. doi:10.1371/journal.pone.0008928 Ejsmont R., Sarov M., Winkler S., Lipinski K., Tomancak P. (2009) A toolkit for high-throughput, cross-species gene engineering in Drosophila. Nature Methods 6, 435 - 437 Saalfeld S., Cardona A., Hartenstein V., Tomancak P. (2009) CATMAID: Collaborative Annotation Toolkit for Massive Amounts of Image Data. Bioinformatics Apr 17. [Epub ahead of print] Preibisch S., Saalfeld S., Tomancak P. (2009) Globally optimal stitching of tiled 3D microscopic image acquisitions. Bioinformatics Jun 1;25(11):1463-5. Lécuyer E., Yoshida H., Parthasarathy N., Alm C., Babak T., Cerovina T., Hughes T.R., Tomancak P., Krause H.M. (2007) Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell Oct 5;131(1):174-87. Tomancak P., Berman B.P., Beaton A., Weiszmann R., Kwan E., Hartenstein V., Celniker S.E., Rubin G.M. (2007) Global analysis of patterns of gene expression during Drosophila embryogenesis. Genome Biol. 8(7):R145. Aboobaker A.A., Tomancak P., Patel N., Rubin G.M., Lai E.C. (2005) Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18017-22 Lai E. C., Tomancak P., Williams R.W., Rubin G. M. (2003) Computational identification of Drosophila microRNA genes. Genome Biol. 4(7):R42 Tomancak P., Beaton A., Weiszmann R., Kwan E., Shu S., Lewis S. E., Richards S., Ashburner M., Hartenstein V., Celniker S. E., Rubin G. M. (2002) Systematic determination of patterns of gene expression during Drosophila embryogenesis. Genome Biol. 3(12):R88
© 2008-2009 MPI-CBG, Imprint, Intranet

Pavel Tomancak

Patterns of gene expression in animal development

Selected Publications