Nuclear signaling by Rac and Rho GTPases is required in the establishment of epithelial planar polarity in the Drosophila eye

Background: The small GTPases Rac and Rho act as cellular switches in many important biological processes. In the fruit fly Drosophila, RhoA participa tes in the establishment of planar polarity, a process mediated by the rece ptor Frizzled (Fz). Thus far, analysis of Rac in this process has not been possible because of the absence of mutant Rac alleles. Here, we have invest igated the role of Rac and Rho in establishing the polarity of ommatidia in the Drosophila eye. Results: By expressing a dominant negative or a constitutively activated fo rm of Rac1,we interfered specifically with Rac signaling and disrupted omma tidial polarity. The resulting defects were similar to the loss/gain-of-fun ction phenotypes typical of tissue-polarity genes. Through genetic interact ion and rescue experiments involving a polarity-specific, loss-of-function dishevelled (dsh) allele, we found that Rac1 acts downstream of Dsh in the Fz signaling pathway, but upstream of, or in parallel to, RhoA. Rac signale d to the nucleus through the Jun N-terminal kinase (JNK) cascade in this pr ocess. By generating point mutations in the effector loop of RhoA, we found that RhoA also signals to the nucleus during the establishment of ommatidi al polarity. Nevertheless, Rac and RhoA activated transcription of distinct target genes, Conclusions: Rac is specifically required downstream of Dsh in the Fz pathw ay. it functions upstream or in parallel to RhoA and both signal to the nuc leus, through distinct effecters, to establish planar polarity in the Droso phila eye.