Genetic evidence that SOST inhibits WNT signaling in the limb

Collette, Nicole M.; Genetos, Damian C.; Murugesh, Deepa; Harland, Richard M.; Loots, Gabriela G.

doi:10.1016/j.ydbio.2010.03.021

Title: Genetic evidence that SOST inhibits WNT signaling in the limb

Journal Article · Tue Mar 30 00:00:00 EDT 2010 · Developmental Biology

DOI:https://doi.org/10.1016/j.ydbio.2010.03.021· OSTI ID:1839869

Collette, Nicole M. ^[1]; Genetos, Damian C. ^[2]; Murugesh, Deepa ^[1]; Harland, Richard M. ^[3]; Loots, Gabriela G. ^[1]

Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Univ. of California, Berkeley, CA (United States)
Univ. of California, Davis, CA (United States)
Univ. of California, Berkeley, CA (United States)

SOST is a negative regulator of bone formation, and mutations in human SOST are responsible for sclerosteosis. In addition to high bone mass, sclerosteosis patients occasionally display hand defects, suggesting that SOST may function embryonically. Here we report that overexpression of SOST leads to loss of posterior structures of the zeugopod and autopod by perturbing anterior–posterior and proximal–distal signaling centers in the developing limb. Mutant mice that overexpress SOST in combination with Grem1 and Lrp6 mutations display more severe limb defects than single mutants alone, while Sost^-/- significantly rescues the Lrp6^-/- skeletal phenotype, signifying that SOST gain-of-function impairs limb patterning by inhibiting the WNT signaling through LRP5/6.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1839869

Report Number(s):: LLNL-JRNL-408192; 366998

Journal Information:: Developmental Biology, Vol. 342, Issue 2; ISSN 0012-1606

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Title: Genetic evidence that SOST inhibits WNT signaling in the limb

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