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

Ju Suk Nam, Emily Park, Taryn J. Turcotte, Servando Palencia, Xiaoming Zhan, Jackie Lee, Kyuson Yun, Walter D. Funk, Jeong Kyo Yoon

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)124-135
Number of pages12
JournalDevelopmental Biology
Volume311
Issue number1
DOIs
Publication statusPublished - Nov 1 2007

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Keywords

  • β-catenin
  • AER
  • Axin2
  • FGF8
  • Limb development
  • R-spondin2
  • shh
  • Wnt

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Nam, J. S., Park, E., Turcotte, T. J., Palencia, S., Zhan, X., Lee, J., ... Yoon, J. K. (2007). Mouse R-spondin2 is required for apical ectodermal ridge maintenance in the hindlimb. Developmental Biology, 311(1), 124-135. https://doi.org/10.1016/j.ydbio.2007.08.023