Furthermore, overexpression of Rspo2 enhanced osteoblastogenesis in vitro.12Rspo3 disruption is embryonic lethal due to angiogenic defects in the murine placenta, though conditional knockout in limb mesenchyme (via Prx1-Cre recombinase-mediated disruption) exacerbated Rspo2 limb malformations in double knockouts.13–15Rspo4 mutations in humans lead to anonychia, but a skeletal phenotype has not been identified.16,17 It is clear that R-spondins influence several aspects of skeletal biology, but their cell-specific roles, particularly in post-natal bone have yet to be elucidated. The gene discussed is RSPO2; the disease is Anonychia.