Apically (left) but not basally (right) targeted wingless mRNA rescues cuticle formation in Drosophila embryos.

Proteins that act at specific cellular locations not only need to be synthesized at the right time but they also need to be transported to the right place. Two solutions exist to this geographical problem: either the proteins are synthesized throughout the cell and then transported to the right location, or the messenger RNA (mRNA) is transported to the right location, where the protein is then translated. The latter approach is less well understood than the former, and is the object of two studies reported in Cell.

Many components of the wingless signalling pathway, including wingless itself, localize apically in polarized cells. Simmonds and colleagues used a sensitive fluorescent in situ hybridization technique and confocal microscopy to study the localization of wingless transcripts in the ectoderm of stage 8 Drosophila melanogaster embryos. They defined two regions in the 3′ untranslated region (UTR) of the mRNA of wingless that act in concert to localize the RNA apically. Using transgenic flies with mutated 3′ UTRs, the authors showed that the apical localization of wingless mRNA and wingless protein is required for signalling through the wingless pathway (see picture).

So, how is the wingless mRNA transported to the apical pole of cells? Wilkie and Davis studied the localization of several apically targeted transcripts in Drosophila syncytial blastoderm embryos, in which thousands of nuclei are aligned in a monolayer and the cytoplasm surrounding them is highly polarized. The authors injected AlexaFluor dye-labelled mRNAs into the basal cytoplasm of the blastoderm embryo, and followed their transport to the apical pole. They found that the mRNAs of wingless and of the pair-rule transcripts runt and fushi tarazu were rapidly incorporated into transport particles and exported out of the nucleus in a non-directional manner. Although different mRNAs were transported in one particle, each transport particle probably contained only a few mRNA molecules. Transport to the apical pole of the blastoderm embryo was rapid and directed, and depended on microtubules, the molecular motor dynein, and the linker protein complex dynactin.

The two studies are complementary, one demonstrating the functional importance of the apical localization of the wingless transcript, and the other presenting a possible mechanism through which this localization is achieved. Although each of the two studies considered only one cell system, similar mechanisms probably operate in many cells in which mRNAs are localized. Many questions remain: what holds together the transport particle? What are the linker molecules connecting the particle and the molecular motor? And, how do these linker molecules interact with dynactin?