Joyner, A. L. — Page 2 | Search bioRxiv

bioRxiv2018

Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons

Outside of the neurogenic niches of the brain, postmitotic neurons have not been found to undergo efficient regeneration. Here we demonstrate that Purkinje cells (PCs), which are born at midgestation and are crucial for both development and function of cerebellar circuits, are rapidly and fully regenerated following their ablation at birth. New PCs are produced by a previously unidentified progenitor population and support normal cerebellum development. The number of PC progenitors and their regenerative capacity, however, diminish soon after birth, and consequently PCs are poorly replenished when ablated at postnatal day 5. Nevertheless, the PC-depleted cerebella reach a normal size by increasing cell size, but scaling of neuron types is disrupted and cerebellar function is impaired. Our findings thus provide a new paradigm in the field of neuron regeneration by identifying a unipotent neural progenitor that buffers against perinatal brain injury in a stage-dependent process.\n\nOne sentence summaryInjury induces a dormant progenitor population present at birth to regenerate cerebellar neurons in a time-dependent manner.

developmental biology↗

bioRxiv2017

Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth

Catch-up growth after insults to growing organs is paramount to achieving robust body proportions. In fly larvae, local injury is followed by local and systemic compensatory mechanisms that allow damaged tissues to regain proportions with other tissues. In vertebrates, local catch-up growth has been described after transient reduction of bone growth, but the underlying cellular responses are controversial. We developed an approach to study catch-up growth in foetal mice by inducing mosaic expression of the cell cycle suppressor p21 in the cartilage cells (chondrocytes) that drive long bone elongation. By specifically targeting the left hindlimb, the right limb served as an internal control. Strikingly, left-right limb symmetry was not altered, revealing deployment of compensatory mechanisms. Above a certain threshold of insult, an orchestrated response was triggered involving local enhancement of bone growth and systemic growth reduction that ensured body proportions were maintained. The local response entailed hyper-proliferation of spared left-limb chondrocytes that was associated with reduced chondrocyte density. The systemic effect involved impaired placental IGF signalling and function, revealing bone-placenta communication. Thus, vertebrates, much like invertebrates, can mount coordinated local and systemic responses to developmental insults to ensure normal body proportions are maintained.

developmental biology↗