RT Journal Article
SR Electronic
T1 Compensatory growth and recovery of tissue cytoarchitecture after transient cartilage-specific cell death in foetal mouse limbs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.06.20.545035
DO 10.1101/2023.06.20.545035
A1 H’ng, Chee Ho
A1 Amarasinghe, Shanika L.
A1 Zhang, Boya
A1 Chang, Hojin
A1 Powell, David
A1 Rosello-Diez, Alberto
YR 2023
UL http://biorxiv.org/content/early/2023/06/20/2023.06.20.545035.abstract
AB A major question in developmental and regenerative biology is how organ size is controlled by progenitor cells. For example, 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 foetal cartilage was repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states was delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death was over, chondroprogenitor differentiation was accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlated with, and was necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.Competing Interest StatementThe authors have declared no competing interest.