Mouse R-spondin2 is required for apical ectodermal ridge maintenance in the hindlimb

The R-spondin (Rspo) family of proteins consists of secreted cysteine-rich proteins that can activate β-catenin signaling via the Frizzled/LRP5/6 receptor complex. Here, we report that targeted inactivation of the mouse Rspo2 gene causes developmental limb defects, especially in the hindlimb. Althou...

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Bibliographic Details
Published in:Developmental biology 2007-11, Vol.311 (1), p.124-135
Main Authors: Nam, Ju-Suk, Park, Emily, Turcotte, Taryn J., Palencia, Servando, Zhan, Xiaoming, Lee, Jackie, Yun, Kyuson, Funk, Walter D., Yoon, Jeong Kyo
Format: Article
Language:English
Subjects:
AER
Animals
Axin2
Catenins - metabolism
Ectoderm - metabolism
Female
FGF8
Hedgehog Proteins - metabolism
Hindlimb - embryology
Limb development
Male
Mice
Mutation
R-spondin2
shh
Signal Transduction
Thrombospondins - genetics
Thrombospondins - metabolism
Wnt
Wnt Proteins - metabolism
β-catenin
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Summary:The R-spondin (Rspo) family of proteins consists of secreted cysteine-rich proteins that can activate β-catenin signaling via the Frizzled/LRP5/6 receptor complex. Here, we report that targeted inactivation of the mouse Rspo2 gene causes developmental limb defects, especially in the hindlimb. Although the initiation of the expression of apical ectodermal ridge (AER)-specific genes, including fibroblast growth factor 8 ( FGF8) and FGF4 occurred normally, the maintenance of these marker expressions was significantly defective in the hindlimb of Rspo2(− /− ) mice. Consistent with the ligand role of R-spondins in the Wnt/β-catenin signaling pathway, expression of Axin2 and Sp8, targets for β-catenin signaling, within AER was greatly reduced in Rspo2(− /− ) embryos. Furthermore, sonic hedgehog ( Shh) signaling within the hindlimbs of Rspo2(− /− ) mice was also significantly decreased. Rspo2 is expressed in the AER of all limb buds, however the stunted phenotype is significantly more severe in the hindlimbs than the forelimbs and strongly biased to the left side. Our findings strongly suggest that Rspo2 expression in the AER is required for AER maintenance likely by regulating Wnt/β-catenin signaling.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2007.08.023