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R-spondin2 expression in the apical ectodermal ridge is essential for outgrowth and patterning in mouse limb
Motoko Aoki1, Hiroshi Kiyonari, Harukazu Nakamura
1Laboratory for Developmental Gene Regulation, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Development, Growth & Differentiation
|December 11, 2007
Summary
Mouse R-spondin2 (Rspo2) is crucial for limb development. Rspo2 deficiency causes severe limb malformations by disrupting apical ectodermal ridge signaling, impacting digit formation and growth.
Area of Science:
- Developmental biology
- Molecular genetics
- Ectodermal development
Background:
- R-spondin2 (Rspo2) is a secreted protein family member with cysteine-rich domains.
- R-spondins activate Wnt/beta-catenin signaling pathways.
- Rspo2 is implicated in embryonic development.
Purpose of the Study:
- To investigate the function of mouse Rspo2 during embryonic limb development.
- To analyze the effects of Rspo2 deficiency on limb patterning and growth.
Main Methods:
- Generation of Rspo2-deficient mice (homozygous mutants).
- Phenotypic analysis of limb development in mutant and wild-type embryos.
- Examination of gene expression patterns, including Fgf8, Fgf4, Sonic hedgehog, and Wnt7a.
Main Results:
- Homozygous mutant forelimbs exhibited defects in distal phalanges and nail structures, with anomalous digit shapes.
- Homozygous mutant hindlimbs displayed more severe malformations, including digit loss and zeugopod component absence.
- Rspo2 deficiency led to reduced Fgf8 expression in the apical ectodermal ridge (AER) and disturbed its dorsoventral patterning.
- Reduced Fgf8, Fgf4 (posterior AER), and Sonic hedgehog (zone of polarizing activity) expression were observed in mutant hindlimbs.
- Expansion of Wnt7a expression towards the ventral side was noted in the dorsal ectoderm of mutant hindlimbs.
Conclusions:
- Rspo2 is essential for maintaining the apical ectodermal ridge (AER) integrity.
- Rspo2 plays a critical role in limb growth and patterning during embryonic development.
- Disruption of Rspo2 impacts key signaling pathways regulating limb formation.
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