Journalists summarize a story's most important facts in one paragraph called a nut graf. Can geneticists summarize the quantity, localization and timing of gene expression in a similarly simplified way? Dupuy et al. report two-dimensional images that represent C. elegans gene expression in both space and time in a recent article in Nature Biotechnology.
C. elegans are transparent. Most of their 959 somatic cells are visible with standard microscopy. The C. elegans genome has been published, and the lineage of most C. elegans cells is fixed.
To take advantage of these properties, the authors generated transgenic C. elegans expressing green fluorescent protein under the control of 1610 unique promoters and analyzed them at various stages of postnatal development in a complex object parametric analysis and sorter (COPAS). For each transgenic animal, COPAS generated a quantitative image profiling fluorescent emission. The authors oriented all of the images horizontally so that their anterior ends faced to the left. In C. elegans, length correlates with age. The authors stacked the images for each transgenic line in length order with the shortest image on top. In the resulting wedge-shaped image stacks, which the authors called 'chronograms', colored stripes indicated the location (horizontal) and timing (vertical) of gene expression.
Tissue-specific promoters generated characteristic chronograms. A single line on the left-hand side of the chronogram represented genes expressed in neurons, such as unc-119. Because vulval muscles develop later than neurons, chronograms of vulval genes, such as egl-15, showed lines starting halfway up the chronogram. The authors averaged the chronograms of more than 40 genes with similar, known expression patterns to produce signature chronograms for each tissue, which they used to determine the localization of uncharacterized genes.
Similar genes had similar gene expression patterns. Genes with statistically correlated chronograms showed nearly identical expression patterns in adult C. elegans and tended to share the same Gene Ontology terms. When the authors arranged genes by their spatiotemporal activities, genes clustered in groups consistent with Gene Ontology, anatomical annotation and microarray data.
In addition to generating a 'localizome' of C. elegans gene expression, the authors suggest that their technique may address more applied questions. Proteins that interact tend to be expressed in the same place at the same time, suggesting that chronograms might help generate a C. elegans interactome.