Wnt signaling plays important roles in skeletal development. However, the activation and function of canonical Wnt signaling in joint development remains unclear. We analyzed the lineage identity and developmental changes of the Wnt-responsive cells during synovial joint formation as well as adulthood in the Wnt signaling reporter TOPgal transgenic mice. At embryonic day (E) 12.5, we found that the TOPgal was inactivated in the presumptive joint forming interzone, but it was intensively activated in the cartilage anlage of developing long bones and digits. At E14.5, the TOPgal activity was found in a subgroup of the articular chondrocyte lineage cells, which were co-immunolabeled with Doublecortin intensively and with Vinculin weakly. At E18.5, the TOPgal/Doublecortin co-immunolabeled cells were found in the superficial layer of the developing articular cartilage. During postnatal development, the TOPgal(+) articular chondrocytes were abundant at P7 and decreased from P10. A small number of TOPgal(+) articular chondrocytes were also found in adult joints. Our study suggests an age- and lineage-specific role of canonical Wnt signaling in joint development and maintenance.

The urothelium is a multilayered epithelium that serves as a barrier between the urinary tract and blood, preventing the exchange of water and toxic substances. It consists of superficial cells specialized for synthesis and transport of uroplakins that assemble into a tough apical plaque, one or more layers of intermediate cells, and keratin 5-expressing basal cells (K5-BCs), which are considered to be progenitors in the urothelium and other specialized epithelia. Fate mapping, however, reveals that intermediate cells rather than K5-BCs are progenitors in the adult regenerating urothelium, that P cells, a transient population, are progenitors in the embryo, and that retinoids are critical in P cells and intermediate cells, respectively, for their specification during development and regeneration. These observations have important implications for tissue engineering and repair and, ultimately, may lead to treatments that prevent loss of the urothelial barrier, a major cause of voiding dysfunction and bladder pain syndrome.