Growth Differentiation Factor

Growth differentiation factors (GDFs) are a subfamily of the TGF-β superfamily, secreted as disulfide-linked dimers processed from pre-pro-proteins, that signal through serine/threonine kinase receptor complexes to SMAD pathways. Numbered GDF1 through GDF15, they display astonishing functional diversity: GDF1, GDF3 and GDF7 pattern the embryonic axis and neural crest; GDF5, GDF6 and GDF7 (BMP-12/13/14) are the cardinal skeletal morphogens governing joint, cartilage and tendon formation, with GDF5 mutations causing brachydactyly and synostosis syndromes; GDF8 (myostatin) is the master negative regulator of skeletal muscle mass; GDF9 and BMP-15 govern oocyte-granulosa communication and female fertility; GDF10 (BMP-3b) modulates bone density and axon guidance; GDF11 drives forebrain development and has controversial roles in aging; GDF15 acts on GFRAL in the brainstem to suppress appetite and mediate sickness anorexia. GDFs are accordingly targeted in muscle wasting (myostatin blockers), osteoarthritis (GDF5) and cachexia (GDF15 axis).