Heparan Sulfate Proteoglycans function as receptors for the R-spondins, a family of growth factors that amplify the strength of WNT signaling during development and in adult stem cells.

In the developing kidney, secreted molecules of the R-spondin family control progenitor cell proliferation and nephron formation by permitting WNT/β-catenin signalling.

R-spondins 2 and 3 can potentiate WNT signaling in the absence of LGRs through interactions with ZNRF3/RNF43 E3 ubiquitin ligases and heparan sulfate proteoglycans, defining two alternative modes of R-spondin-mediated signaling.

R-spondin3 global haplo-insufficiency or its deletion in pre-osteoblasts lead to gain of bone mass in the appendicular skeleton with no or opposite phenotype in the axial skeleton.

Wnt/β-Catenin independent role of Rspo1 in physiological condition is revealed.

Sox8 can induce female-to-male sex reversal of the R-spondin1 loss-of-function mouse mutants in the absence of Sox9..

A systematic genetic analysis comprising seven genome-wide screens in haploid human cells uncovered new regulatory mechanisms at most levels in the WNT signaling pathway.

HGF-MET signaling phosphorylates- and PTPRK dephosphorylates ZNRF3 to regulate ZNRF3 internalization, functioning as a rheostat for Wnt signaling.

Two cancer related proteins, tyrosine phosphatase PTPRK and ubiquitin ligase ZNRF3, interact to downregulate Wnt receptors, thereby regulating Spemann organizer function during Xenopus development.

A novel targeted protein degradation system to achieve cell-type-specific enhancement of Wnt signaling.