Which factor is essential for joint formation in limbs?
Joint formation requires interruption of continuous chondrogenesis to create interzones with distinct fate. Cells at future joint sites downregulate Sox9 and collagen II, express Wnt14 Wnt4, GDF5 and increase hyaluronan production to prevent differentiation and promote cavitation and synovium formation. GDF5, also called cartilage-derived morphogenetic protein-1, a BMP family ligand, promotes joint specification, maintains interzone integrity, and recruits surrounding cells to form articular cartilage. Mutations in GDF5 cause brachydactyly type C and joint fusions. BMP4 promotes cartilage and apoptosis, SHH patterns AP, FGF8 drives proliferation.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: GDF5 in joint formation and interzone.