Genetic evidence that SOST inhibits WNT signaling in the limb

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

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)169-179
Number of pages11
JournalDevelopmental Biology
Volume342
Issue number2
DOIs
StatePublished - Jun 2010

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Extremities
Mutation
Osteogenesis
Hand
Phenotype
Bone and Bones
Sclerosteosis

Keywords

  • Limb formation
  • Sclerostin
  • Shh
  • SOST
  • WNT signaling

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Genetic evidence that SOST inhibits WNT signaling in the limb. / Collette, Nicole M.; Genetos, Damian C; Murugesh, Deepa; Harland, Richard M.; Loots, Gabriela G.

In: Developmental Biology, Vol. 342, No. 2, 06.2010, p. 169-179.

Research output: Contribution to journalArticle

Collette, NM, Genetos, DC, Murugesh, D, Harland, RM & Loots, GG 2010, 'Genetic evidence that SOST inhibits WNT signaling in the limb', Developmental Biology, vol. 342, no. 2, pp. 169-179. https://doi.org/10.1016/j.ydbio.2010.03.021
Collette, Nicole M. ; Genetos, Damian C ; Murugesh, Deepa ; Harland, Richard M. ; Loots, Gabriela G. / Genetic evidence that SOST inhibits WNT signaling in the limb. In: Developmental Biology. 2010 ; Vol. 342, No. 2. pp. 169-179.
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