title: Nuclear signaling by Rac and Rho GTPases is required in the establishment of epithelial planar polarity in the Drosophila eye.
abstract: BACKGROUND
  The small GTPases Rac and Rho act as cellular switches in many important biological processes. In the fruit fly Drosophila, RhoA participates in the establishment of planar polarity, a process mediated by the receptor 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 investigated 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 form of Rac1, we interfered specifically with Rac signaling and disrupted ommatidial polarity. The resulting defects were similar to the loss/gain-of-function phenotypes typical of tissue-polarity genes. Through genetic interaction 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 signaled to the nucleus through the Jun N-terminal kinase (JNK) cascade in this process. By generating point mutations in the effector loop of RhoA, we found that RhoA also signals to the nucleus during the establishment of ommatidial polarity. Nevertheless, Rac and RhoA activated transcription of distinct target genes.
  
  
  CONCLUSIONS
  Rac is specifically required downstream of Dsh in the Fz pathway. It functions upstream or in parallel to RhoA and both signal to the nucleus, through distinct effectors, to establish planar polarity in the Drosophila eye.
authors.affiliation: EMBL, Developmental Biology Programme, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Fanto
authors.forename: U
authors.initials: U
authors.lastname: Weber
authors.forename: D I
authors.initials: DI
authors.lastname: Strutt
authors.forename: M
authors.initials: M
authors.lastname: Mlodzik
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D004847:Epithelial Cells / Q000502:physiology; D005123:Eye / Q000254:growth & development; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D010750:Phosphoproteins; C000606588:dsh protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein