Identification of tightly regulated groups of genes during Drosophila melanogaster embryogenesis

Abstract

Time-series analysis of whole-genome expression data during Drosophila melanogaster development indicates that up to 86% of its genes change their relative transcript level during embryogenesis. By applying conservative filtering criteria and requiring 'sharp' transcript changes, we identified 1534 maternal genes, 792 transient zygotic genes, and 1053 genes whose transcript levels increase during embryogenesis. Each of these three categories is dominated by groups of genes where all transcript levels increase and/or decrease at similar times, suggesting a common mode of regulation. For example, 34% of the transiently expressed genes fall into three groups, with increased transcript levels between 2.5-12, 11-20, and 15-20 h of development, respectively. We highlight common and distinctive functional features of these expression groups and identify a coupling between downregulation of transcript levels and targeted protein degradation. By mapping the groups to the protein network, we also predict and experimentally confirm new functional associations.

Figure 1

(A) Increase and decrease of fly gene transcript levels during embryogenesis. Red bars indicate points of sharp expression changes from low to high and blue bars signify changes from high to low expression. (B) Distribution of embryo stages at sampling times. For instance, at 12 h, a majority of embryos have reached stages 12–13. Samples are taken every half an hour at the start of the study.

Figure 2

Major classes of transcript levels, as determined by global convolution. Arcs represent the dominant subgroups within class I, II, and III transcripts. For instance, class I is dominated by two main subgroups I:a and I:b, represented by the pink and red arcs, respectively. Time is in hours, and yellow rectangles signify measurement points. The time of increase and decrease of the transcript groups coincides with those derived by local convolution (Supplementary Figure S1). Note the interplay between groups as a decrease of one transcript group is followed by an increase of another.

Figure 3

Major component of a literature-derived protein interaction subnetwork, obtained from the String database at a reliability score of at least 0.3 (von Mering et al, 2005). It reveals that several well-known interacting proteins also show similar expression profiles. Examples are the highlighted vacuolar ATPases, the proteasome, or interactors of Peter Pan. Notch appears as the central node of the network and contributes to the high interconnectivity of the (transient) class II:a group. Some genes with expression profiles very similar to Notch (labeled by red arrows) are currently only loosely associated with the pathway (see text), but might share more functionality with Notch than previously thought. Notch is labeled for reference purposes. Note that unassigned in the legend means that the respective genes belong to the class but not to any of the major subclasses. To explore this complex network in full detail, see the interactive figure and data files in Supplementary information.

Figure 4

Decline of transcript levels of four class II:a genes as predicted by the array analysis. Transcript levels are high until stage 12, but decline rapidly after stage 13.

Figure 5

Spatial colocalization of worniu, pdm2, CG13333 and CG4440 with Delta in embryos stage 11–12. Columns 1 and 2 show stainings individually and column 3 shows colocalization. CG4440 exhibits an anti-correlation, suggesting colocalization with Notch rather than Delta.