Critical thresholds of Bmp and Tgfβ signaling in joint development. (a, b) Histological sections stained with hematoxylin and eosin show the different layers of joint cartilage in a human knee (16-year-old) and juvenile spotted gar jaw. (c) The levels, duration, and/or type of Bmp signaling help to specify the different types of chondrocytes at and around joints: hypertrophic, radial, transitional, and superficial. The Bmp ligands Gdf5/6/7 and antagonists Chordin (Chd), Noggin (Nog), and Gremlin2 (Grem2) are expressed in the developing interzone, and Bmp2/4/7 have been reported to be expressed either at a distance from the joint or at the joint itself. Variable diffusion of these ligands and antagonists may establish different levels of Bmp signaling, and signaling through Bmpr1a and Bmpr1b receptors could also influence joint fate. TGFβ signaling also has an important role to specify joint fates, with the Tgfbr2 receptor enriched at developing joints.