Rho-kinase regulates tissue morphogenesis via non-muscle myosin and LIM-kinase during Drosophila development.
BACKGROUND
The Rho-kinases (ROCKs) are major effector targets of the activated Rho GTPase that have been implicated in many of the Rho-mediated effects on cell shape and movement via their ability to affect acto-myosin contractility. The role of ROCKs in cell shape change and motility suggests a potentially important role for Rho-ROCK signaling in tissue morphogenesis during development. Indeed, in Drosophila, a single ROCK ortholog, DRok, has been identified and has been found to be required for establishing planar cell polarity.


RESULTS
We have examined a potential role for DRok in additional aspects of tissue morphogenesis using an activated form of the protein in transgenic flies. Our findings demonstrate that DRok activity can influence multiple morphogenetic processes, including eye and wing development. Furthermore, genetic studies reveal that Drok interacts with multiple downstream effectors of the Rho GTPase signaling pathway, including non-muscle myosin heavy chain, adducin, and Diaphanous in those developmental processes. Finally, in overexpression studies, we determined that Drok and Drosophila Lim-kinase interact in the developing nervous system.


CONCLUSIONS
These findings indicate widespread diverse roles for DRok in tissue morphogenesis during Drosophila development, in which multiple DRok substrates appear to be required.
Verdier
Valerie
V
Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA. vlrverdier@yahoo.com <vlrverdier@yahoo.com>
Guang-Chao-Chen
Settleman
Jeffrey
J
D000818:Animals; D004330:Drosophila / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins / Q000235:genetics*; D005123:Eye / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D054461:Lim Kinases; D009024:Morphogenesis; D009420:Nervous System / Q000254:growth & development; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics*; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014921:Wings, Animal / Q000254:growth & development; D020741:rho GTP-Binding Proteins / Q000235:genetics; D054460:rho-Associated Kinases
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases; D054461:Lim Kinases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D024501:Nonmuscle Myosin Type IIB; D020741:rho GTP-Binding Proteins