2005
DOI: 10.1016/j.devcel.2005.01.003
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Shifted, the Drosophila Ortholog of Wnt Inhibitory Factor-1, Controls the Distribution and Movement of Hedgehog

Abstract: We here identify and characterize an extracellular modulator of Hedgehog signaling in Drosophila, Shifted. Shifted is required for high levels of long-range signaling in the developing wing imaginal disc. Surprisingly, shifted encodes the only Drosophila ortholog of the secreted vertebrate protein Wnt Inhibitory Factor-1 (WIF-1), whose known role is to bind to extracellular Wnts and inhibit their activity. However, Shifted does not regulate Hedgehog signaling by affecting Wingless or Wnt signaling. We show ins… Show more

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Cited by 113 publications
(171 citation statements)
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“…2 I). Similar specific destabilization of lipid modified Hh in the extracellular matrix has been observed both in HSPG and shf mutants (15)(16)(17)(18)(19)(20). All together these results suggest that Hh lipid modifications are necessary for Hh packaging with Lp to interact with the extracellular matrix components or that Lp could stabilise the binding of Hh to HSPGs.…”
Section: Results and Discusionsupporting
confidence: 74%
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“…2 I). Similar specific destabilization of lipid modified Hh in the extracellular matrix has been observed both in HSPG and shf mutants (15)(16)(17)(18)(19)(20). All together these results suggest that Hh lipid modifications are necessary for Hh packaging with Lp to interact with the extracellular matrix components or that Lp could stabilise the binding of Hh to HSPGs.…”
Section: Results and Discusionsupporting
confidence: 74%
“…The emerging theme is that the cholesterol and palmitate moieties help generate a steep Hh gradient across the extracellular matrix of a morphogenetic field by restricting Hh dilution and unregulated diffusion (13). In this context, it has been described that the HSPGs and Shifted, a component of the extracellular matrix, are important for stabilization and spreading of only the lipid-modified Hh (14)(15)(16)(17)(18)(19)(20).…”
mentioning
confidence: 99%
“…Thus, human Wif-1 (WIF1) is downregulated in cancers (Mazieres et al, 2004;Kansara et al, 2009) and the mouse Wif1 knockout accelerates the development of radiation-induced osteosarcomas in vivo (Kansara et al, 2009). Furthermore, overexpression of human WIF1 inhibits the growth of cells from lung and bladder cancers (Lin et al, 2006;Tang et al, 2009).In Drosophila, the extracellular matrix (ECM) component Shifted (Shf), which is the ortholog of vertebrate Wif-1, is implicated in Hh signaling (Glise et al, 2005;Gorfinkiel et al, 2005). In the absence of Shf there is no Hh gradient formation, the expression of Hh target genes is reduced and the levels of extracellular Hh are much reduced.…”
mentioning
confidence: 99%
“…Interestingly, Drosophila Shf and vertebrate Wif-1 functions also exhibit similarities in Wg and Hh signaling. Shf has no detectable role in Wnt signaling; overexpression of Shf does not generate Wnt-related defects, and neither the misexpression of various Wnts nor of the Wg signaling component Dishevelled (Dsh) can reproduce the shf phenotype (Glise et al, 2005). However, expression of the human WIF1 protein in the Drosophila wing disc blocks Wg signaling but does not rescue the shf mutant phenotype (Gorfinkiel et al, 2005).…”
mentioning
confidence: 99%
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