R-spondins (Rspo) are a recently discovered secretory protein family with four members in human and mouse. We and others demonstrated that R-spondins can activate canonical Wnt signaling and beta-catenin-dependent gene expression. Our study further demonstrated that R-spondins are novel ligands for the Frizzled8 and LRP6 (LDL-receptor-related protein 6) receptors. To gain insight into their biological functions, the RNA expression pattern of the mouse R-spondin family genes was analyzed during mouse development. Our study shows that R-spondin gene transcripts are widely expressed with distinct patterns in mouse at different developmental stages.