Mice keep limbs even
A mouse study has found that if something goes wrong with a limb during development, placenta slows the growth of the rest to keep them even.
Maintaining equal growth rates in opposing limbs is crucial for animals to achieve a symmetrical adult form, and researchers in the US wanted to what happens if something goes wrong with one limb during development.
According to their new paper, the team from the Sloan Kettering Institute found mice can stimulate local growth while suppressing overall growth.
This allows damaged tissue to catch-up with other tissue, and makes sure that bones in opposite limbs lengthen together when one is injured.
It is already known that insects do a similar thing by combining compensatory proliferation in the injured body part and growth delay in other parts of the body, but in vertebrates the corresponding responses have not been clear.
To explore how coordinated growth is achieved in vertebrates, the authors engineered mice to express a cell cycle suppressor, shortly before birth, specifically in bone-forming cartilage cells in one hind limb, but not the other.
This allowed them to inhibit bone growth on one side while maintaining normal growth on the other side.
On the inhibited side, they further limited the expression of the suppressor to only some of the bone-forming cells, allowing them to examine the responses of unsuppressed cells on the same side.
They found that, within the targeted cartilage, those cells not producing the cell-cycle suppressor proliferated more than normal, so that overall growth on the affected side was only mildly slowed.
The signal that drove this hyperproliferation is not yet clear, but the authors found that, once a certain injury threshold was surpassed, the response was proportional to the number of cells that had been suppressed.
They further found that, in response to the local slowing of growth, there was a systemic reduction in rate of growth that correlated with an impairment of insulin-like growth factor signalling in the placenta, which, the authors suggest, likely acts as a central regulator of overall growth rate and body proportions during development.
Noting the similarities between growth regulation mechanisms between insects and vertebrates, the authors said; “These results reveal that the response to developmental insults is quite evolutionarily conserved, and open new avenues of future research and to develop therapies for growth disorders”.