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. 2006 Feb;10(2):187-97.
doi: 10.1016/j.devcel.2005.12.013.

Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway

Jessica Svärd  1 , Karin Heby-Henricson, Madelen Persson-Lek, Björn Rozell, Matthias Lauth, Asa Bergström, Johan Ericson, Rune Toftgård, Stephan Teglund
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Free article

Genetic elimination of Suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway

Jessica Svärd et al. Dev Cell. 2006 Feb.
Free article

Erratum in

  • Dev Cell. 2006 Mar;10(3):409. Henricson, Karin Heby [corrected to Heby-Henricson, Karin]

Abstract

The Hedgehog (Hh) pathway plays important roles during embryogenesis and carcinogenesis. Here, we show that ablation of the mouse Suppressor of fused (Sufu), an intracellular pathway component, leads to embryonic lethality at approximately E9.5 with cephalic and neural tube defects. Fibroblasts derived from Sufu(-/-) embryos showed high Gli-mediated Hh pathway activity that could not be modulated at the level of Smoothened and could only partially be blocked by PKA activation. Despite the robust constitutive pathway activation in the Sufu(-/-) fibroblasts, the GLI1 steady-state localization remained largely cytoplasmic, implying the presence of an effective nuclear export mechanism. Sufu(+/-) mice develop a skin phenotype with basaloid changes and jaw keratocysts, characteristic features of Gorlin syndrome, a human genetic disease linked to enhanced Hh signaling. Our data demonstrate that, in striking contrast to Drosophila, in mammals, Sufu has a central role, and its loss of function leads to potent ligand-independent activation of the Hh pathway.

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