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R‐spondin2 expression in the apical ectodermal ridge is essential for outgrowth and patterning in mouse limb development
Author(s) -
Aoki Motoko,
Kiyonari Hiroshi,
Nakamura Harukazu,
Okamoto Hitoshi
Publication year - 2008
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/j.1440-169x.2007.00978.x
Subject(s) - apical ectodermal ridge , zone of polarizing activity , ectoderm , limb development , biology , limb bud , forelimb , sonic hedgehog , wnt signaling pathway , fgf8 , anatomy , microbiology and biotechnology , embryogenesis , genetics , fibroblast growth factor , signal transduction , embryo , receptor
Mouse R‐spondin2 (Rspo2) is a member of the R‐spondin protein family, which is characterized by furin‐like cysteine‐rich domains and a thrombospondin type 1 repeat. R‐spondin is a secreted molecule that activates Wnt/ β ‐catenin signaling. Rspo2 ‐deficient mice were generated to investigate the function of mouse Rspo2 during embryonic development. The homozygous mutant forelimb showed defects in distal phalanges and nail structures, and the digits were anomalous in shape. The homozygous mutant hindlimb showed more severe malformations, including lack of digits and zeugopod components. Rspo2 is expressed in the apical ectodermal ridge (AER) of the developing limb. Fgf8 expression in the AER was significantly lower in the homozygous mutant forelimb than in the wild‐type forelimb and it was disturbed along the dorsoventral axis. In the homozygous mutant hindlimb, Fgf8 and Fgf4 expression in the posterior AER and Sonic hedgehog expression in the zone of polarizing activity (ZPA) were reduced. The homozygous mutant hindlimb also showed expansion of Wnt7a expression in the dorsal ectoderm toward the ventral side. This study shows that Rspo2 is critical for maintenance of the AER and for growth and patterning in limb development.