TY - JOUR
T1 - Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development
AU - Skouloudaki, Kassiani
AU - Puetz, Michael
AU - Simons, Matias
AU - Courbard, Jean Remy
AU - Boehlke, Christopher
AU - Hartleben, Björn
AU - Engel, Christina
AU - Moeller, Marcus J.
AU - Englert, Christoph
AU - Bollig, Frank
AU - Schäfer, Tobias
AU - Ramachandran, Haribaskar
AU - Mlodzik, Marek
AU - Huber, Tobias B.
AU - Kuehn, E. Wolfgang
AU - Kim, Emily
AU - Kramer-Zucker, Albrecht
AU - Walz, Gerd
PY - 2009/5/26
Y1 - 2009/5/26
N2 - 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.
AB - 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.
KW - Fat
KW - Planar cell polarity
KW - Polycystic kidney disease
UR - http://www.scopus.com/inward/record.url?scp=66649130741&partnerID=8YFLogxK
U2 - 10.1073/pnas.0811691106
DO - 10.1073/pnas.0811691106
M3 - Article
C2 - 19439659
AN - SCOPUS:66649130741
SN - 0027-8424
VL - 106
SP - 8579
EP - 8584
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -