PUBLICATION

Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development

Authors
Skouloudaki, K., Puetz, M., Simons, M., Courbard, J.R., Boehlke, C., Hartleben, B., Engel, C., Moeller, M.J., Englert, C., Bollig, F., Schäfer, T., Ramachandran, H., Mlodzik, M., Huber, T.B., Kuehn, E.W., Kim, E., Kramer-Zucker, A., and Walz, G.
ID
ZDB-PUB-090518-16
Date
2009
Source
Proceedings of the National Academy of Sciences of the United States of America   106(21): 8579-8584 (Journal)
Registered Authors
Bollig, Frank
Keywords
Fat, planar cell polarity, polycystic kidney disease
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cadherins/genetics
  • Cadherins/metabolism
  • Cell Line
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Humans
  • Kidney/embryology*
  • Kidney/metabolism*
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Microtubule-Associated Proteins/genetics
  • Microtubule-Associated Proteins/metabolism
  • Promoter Regions, Genetic/genetics
  • Protein Binding
  • Protein Serine-Threonine Kinases/genetics
  • Protein Serine-Threonine Kinases/metabolism*
  • Signal Transduction*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
19439659 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Spatial organization of cells and their appendages is controlled by the planar cell polarity pathway, a signaling cascade initiated by the protocadherin Fat in Drosophila. Vertebrates express 4 Fat molecules, Fat1-4. We found that depletion of Fat1 caused cyst formation in the zebrafish pronephros. Knockdown of the PDZ domain containing the adaptor protein Scribble intensified the cyst-promoting phenotype of Fat1 depletion, suggesting that Fat1 and Scribble act in overlapping signaling cascades during zebrafish pronephros development. Supporting the genetic interaction with Fat1, Scribble recognized the PDZ-binding site of Fat1. Depletion of Yes-associated protein 1 (YAP1), a transcriptional co-activator inhibited by Hippo signaling, ameliorated the cyst formation in Fat1-deficient zebrafish, whereas Scribble inhibited the YAP1-induced cyst formation. Thus, reduced Hippo signaling and subsequent YAP1 disinhibition seem to play a role in the development of pronephric cysts after depletion of Fat1 or Scribble. We hypothesize that Hippo signaling is required for normal pronephros development in zebrafish and that Scribble is a candidate link between Fat and the Hippo signaling cascade in vertebrates.
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