Acknowledgements: We thank Jonathan Gleadle, Vincent Wong and Darling Rojas-Canales for inspiring discussions about mTORC1 and the balance between proliferation and cell size in compensatory responses. We also acknowledge the Monash Bioinformatics Platform (especially Kirill Tsyganov), and Trevor Wilson, at the Medical Genomics Facility, Monash Health Translation Precinct, for their excellent technical help. This study is funded by HFSP CDA00021/2019-C (to A.R-D.) and NHMRC Ideas grant 2002084 (to C.H.H. and A.R-D.). The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government.A major question in developmental and regenerative biology is how organ size and architecture are controlled by progenitor cells. While limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse fetal cartilage is repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states is delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death is over, chondroprogenitor differentiation is accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlates with, and is necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies
