Building an Atlas of Spatial Gene Expression in the Fruit Fly Embryo
work with the BDTNP Imaging Group at LBL
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
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.
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
- 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",
Research Conference, San Diego, CA, (April 2005). [pdf]