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Scribble Participates in Hippo Signaling and is Required for Normal Zebrafish Pronephros Development

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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References
1.
Wada H, Iwasaki M, Sato T, Masai I, Nishiwaki Y, Tanaka H . Dual roles of zygotic and maternal Scribble1 in neural migration and convergent extension movements in zebrafish embryos. Development. 2005; 132(10):2273-85. DOI: 10.1242/dev.01810. View

2.
Willecke M, Hamaratoglu F, Kango-Singh M, Udan R, Chen C, Tao C . The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size. Curr Biol. 2006; 16(21):2090-100. DOI: 10.1016/j.cub.2006.09.005. View

3.
Cho E, Feng Y, Rauskolb C, Maitra S, Fehon R, Irvine K . Delineation of a Fat tumor suppressor pathway. Nat Genet. 2006; 38(10):1142-50. DOI: 10.1038/ng1887. View

4.
Eggenschwiler J, Anderson K . Cilia and developmental signaling. Annu Rev Cell Dev Biol. 2007; 23:345-73. PMC: 2094042. DOI: 10.1146/annurev.cellbio.23.090506.123249. View

5.
Hariharan I, Bilder D . Regulation of imaginal disc growth by tumor-suppressor genes in Drosophila. Annu Rev Genet. 2006; 40:335-61. DOI: 10.1146/annurev.genet.39.073003.100738. View