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

Kassiani Skouloudaki, Michael Puetz, Matias Simons, Jean Remy Courbard, Christopher Boehlke, Björn Hartleben, Christina Engel, Marcus J. Moeller, Christoph Englert, Frank Bollig, Tobias Schäfer, Haribaskar Ramachandran, Marek Mlodzik, Tobias B. Huber, E. Wolfgang Kuehn, Emily Kim, Albrecht Kramer-Zucker, Gerd Walz

Research output: Contribution to journalArticlepeer-review

130 Scopus citations

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.

Original languageEnglish
Pages (from-to)8579-8584
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number21
DOIs
StatePublished - 26 May 2009

Keywords

  • Fat
  • Planar cell polarity
  • Polycystic kidney disease

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