Fig. 2

Proteoglycan 4 (Prg4) is required for bone morphogenetic protein 9 (BMP9)-induced cavitation. a–d In situ hybridization for Prg4 expression. a Prg4 is expressed by cells lining the P2/P3 synovial cavity (arrowhead) and forming the superficial layer of the articular cartilage of the neonatal joint at PN10. b In BMP9-treated cavity-forming digits, Prg4 is expressed by cells lining the induced cavity (arrow) and by cells forming the chondrogenic nodule (arrowhead) 72 h after treatment. c At 7 days after treatment with a BMP9 bead, Prg4 is expressed by cells lining the cavity on both the stump side (arrowhead) and the nodule side (arrow). d At 24 h after BMP9 treatment, Prg4 transcripts are found localized in clusters of cells in the wound bed (arrowhead) associated with the initiation of the cavitation response. e, f Control bovine serum albumin (BSA) bead implantation does not induce an articulation response in PRG4^+/− (e) or PRG4^−/− (f) digit amputations. g BMP9 treatment of PRG4^+/- digit amputations induces an articulation response that includes a distal nodule and cavity. h No regeneration response is observed after BMP9 treatment in PRG4^−/− mutants. i–m In situ hybridization of chondrogenic genes expressed at the distal stump in non-cavity-forming PRG4^−/− mutant digits 72 h after BMP9 treatment. i Col2a1. j Sox9. k Acan. l Fmod. m Ucma. Distal is to the right and dorsal is to the top; n nodule, c cavity, s stump, * indicates bead. Scale bars: a–d, i–m = 100 µm; e–h = 200 µm