The Drosophila ortholog of the human Wnt inhibitor factor Shifted controls the diffusion of lipid-modified Hedgehog

被引：103

作者：

Gorfinkiel, N ^{[1
]}

Sierra, J ^{[1
]}

Callejo, A ^{[1
]}

Ibañez, C ^{[1
]}

Guerrero, I ^{[1
]}

机构：

[1] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain

来源：

DEVELOPMENTAL CELL | 2005年 / 8卷 / 02期

关键词：

D O I：

10.1016/j.devcel.2004.12.018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Hedgehog (Hh) family of morphogenetic proteins has important instructional roles in metazoan development and human diseases. Lipid modified Hh is able to migrate to and program cells far away from its site of production despite being associated with membranes. To investigate the Hh spreading mechanism, we characterized Shifted (Shf) as a component in the Drosophila Hh pathway. We show that Shf is the ortholog of the human Wnt inhibitory factor (WIF), a secreted antagonist of the Wingless pathway. In contrast, Shf is required for Hh stability and for lipid-modified Hh diffusion. Shf colocalizes with Hh in the extracellular matrix and interacts with the heparan sulfate proteoglycans (HSPG), leading us to suggest that Shf could provide HSPG specificity for Hh. We also show that human WIF inhibits Wg signaling in Drosophila without affecting the Hh pathway, indicating that different WIF family members might have divergent functions in each pathway.

引用

页码：241 / 253

页数：13

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