[index]

Building an Atlas of Spatial Gene Expression in the Fruit Fly Embryo



work with the BDTNP Imaging Group at LBL

Abstract:


The output of animal gene transcription networks are complex 3D patterns of expression. These dynamically changing patterns of expression may vary radically from one cell to the next and it's these spatial variations which define and determine the shape and behavior of the animal. It is a grand challenge of biology to learn how to decipher the transcriptional information in the genome to the point where we can predict and model such intricate patterns.

Researchers typically analyze spatial patterns of gene expression in multicellular organisms by visual inspection of photographic images of in situ hybridization experiments. A profound limitation of this approach is that it captures little 3D structure and typically provides only rough quantitative information. If we are to fully describe and understand animals, we first need a means to quantitatively record, with cellular resolution, these phenomenally complex expression patterns.

We are developing approaches to combining expression levels of multiple gene products recorded from different developing fruit fly embryos (Drosophila melanogaster). 2-photon laser scanning microscopy is a key enabling technology which allows measurement of relative concentrations of gene products inside a 3D volume. However, it can only provide information about 2 or 3 gene products in a given animal. Our contribution is a method for registering data from different embryos stained with overlapping subsets of fluorescent tags in order to build a composite map, ultimately containing 1000s of genes. We formulate this as a 3D deformable template matching problem and in order to overcome significant distortions in the shapes of embryos as well as biological variation in morphology and different numbers of cells.


Abstracts/Papers:

  • C. Fowlkes, C. Luengo Hendriks, S. Keränen, G. Weber, O. Rübel, M-Y Huang, S. Chatoor, L. Simirenko, C. Henriquez, A. Beaton, R. Weiszmann, S. Celniker, M. Eisen, B. Hamann, D. Knowles, M. Biggin, J. Malik. "Constructing a quantitative spatio-temporal atlas of gene expression in the Drosophila blastoderm", submitted

  • C. Luengo-Hendriks, S. Keränen, C. Fowlkes, L. Simirenko, G. Weber, C. Henriquez, D. Kaszuba, B. Hamann, M. Eisen, J. Malik, D. Sudar, M. Biggin D. Knowles, ``3D Morphology and Gene Expression in the Drosophila Blastoderm at Cellular Resolution I: Data Acquisition Pipeline'', Genome Biology, [pdf]

  • C. Fowlkes, C. Luengo Hendriks, S. Keräanen, M. Biggin, D. Knowles, D. Sudar, J. Malik. "Registering Drosophila Embryos at Cellular Resolution to Build a Quantitative 3D Map of Gene Expression Patterns and Morphology", CSB 2005 Workshop on BioImage Data Minning and Informatics, Palo Alto, CA, (August 2005). [pdf]

  • C. Fowlkes, C. Luengo Hendriks, S. Keränen, M. Biggin, D. Knowles, D. Sudar, J. Malik. "Building Composite Maps of Gene Expression Patterns and Morphology: Registering 3D Representations of Drosophila Embryos", 46th Drosophila Research Conference, San Diego, CA, (April 2005). [pdf]