Dev108811 2848..2854

Much of the mammalian skeleton is derived from a cartilage template that undergoes rapid growth during embryogenesis, but the molecular mechanism of growth regulation is not well understood. Signaling by mammalian target of rapamycin complex 1 (mTORC1) is an evolutionarily conservedmechanism that controls cellular growth. Here we report that mTORC1 signaling is activated during limb cartilage development in the mouse embryo. Disruption of mTORC1 signaling through deletion of either mTOR or the associated protein Raptor greatly diminishes embryonic skeletal growth associated with severe delays in chondrocyte hypertrophy and bone formation. The growth reduction of cartilage is not due to changes in chondrocyte proliferation or survival, but is caused bya reduction in cell size and in the amount of cartilagematrix.Metabolic labeling revealsanotable deficit in the rateof protein synthesis in Raptor-deficient chondrocytes. Thus, mTORC1 signaling controls limb skeletal growth through stimulation of protein synthesis in chondrocytes.