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

被引:97
作者
Nam, Ju-Suk
Park, Emily
Turcotte, Taryn J.
Palencia, Servando
Zhan, Xiaoming
Lee, Jackie
Yun, Kyuson
Funk, Walter D.
Yoon, Jeong Kyo
机构
[1] Maine Med Ctr, Res Inst, Ctr Mol Med, Scarborough, ME 04074 USA
[2] Nuvelo Inc, San Carlos, CA 94070 USA
[3] Jackson Lab, Bar Harbor, ME 04609 USA
关键词
R-spondin2; Wnt; beta-catenin; axin2; FGF8; shh; AER; limb development;
D O I
10.1016/j.ydbio.2007.08.023
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The R-spondin (Rspo) family of proteins consists of secreted cysteine-rich proteins that can activate beta-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/beta-catenin signaling pathway, expression of Axing and Sp8, targets for R-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/beta-catenin signaling. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:124 / 135
页数:12
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