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Science 24 December 2004:
Vol. 306. no. 5705, pp. 2264 - 2267
DOI: 10.1126/science.1104193
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Reports

ß-Arrestin 2 Regulates Zebrafish Development Through the Hedgehog Signaling Pathway

Alyson M. Wilbanks,1,4 Gregory B. Fralish,1,4 Margaret L. Kirby,3 Larry S. Barak,1,4 Yin-Xiong Li,1,2,3* Marc G. Caron1,2,4*

ß-arrestins are multifunctional proteins that act as scaffolds and transducers of intracellular signals from heptahelical transmembrane-spanning receptors (7TMR). Hedgehog (Hh) signaling, which uses the putative 7TMR, Smoothened, is established as a fundamental pathway in development, and unregulated Hh signaling is associated with certain malignancies. Here, we show that the functional knockdown of ß-arrestin 2 in zebrafish embryos recapitulates the many phenotypes of Hh pathway mutants. Expression of wild-type ß-arrestin 2, or constitutive activation of the Hh pathway downstream of Smoothened, rescues the phenotypes caused by ß-arrestin 2 deficiency. These results suggest that a functional interaction between ß-arrestin 2 and Smoothened may be critical to regulate Hh signaling in zebrafish development.

1 Department of Cell Biology, Center for Models of Human Disease, Institute for Genome Science and Policy, Duke University Medical Center, Durham, NC 27710, USA.
2 Department of Medicine, Center for Models of Human Disease, Institute for Genome Science and Policy, Duke University Medical Center, Durham, NC 27710, USA.
3 Department of Pediatrics, Center for Models of Human Disease, Institute for Genome Science and Policy, Duke University Medical Center, Durham, NC 27710, USA.
4 Howard Hughes Medical Institute Laboratories, Center for Models of Human Disease, Institute for Genome Science and Policy, Duke University Medical Center, Durham, NC 27710, USA.

* To whom correspondence should be addressed. E-mail: caron002{at}mc.duke.edu (M.G.C.); lyx{at}duke.edu (Y.-X.L.)

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