Biology subjects

Cura Costa, E.

Publications and source records attributed to Cura Costa, E..

3 recordsLinked to original sources

bioRxiv2024

Local control of cellular proliferation underlies neuromast regeneration in zebrafish

Biological systems are never in equilibrium but maintain stability despite continuous external disturbances. A prime example of this is organ regeneration, where, despite intrinsically stochastic damage, organs are rebuilt through controlled cellular proliferation. In this study, we employ a cell- based computational modelling approach to investigate the proliferative response to injury. We developed a minimal two-dimensional Cellular Potts Model (CPM) using empirical data from regenerating neuromasts in larval zebrafish. Remarkably, the CPM both qualitatively and quantitatively recapitulates the regenerative response of neuromasts following laser-mediated cell ablation. Assuming that cell proliferation is locally regulated by a delayed switch, mitotic activity ceases once the type-dependent number of neighbouring cells exceeds a deterministic critical threshold. An intriguing corollary of our findings is that a local negative feedback loop among identical cells may represent a general mechanism underlying organ-level proportional homeostasis.

developmental biology↗

bioRxiv2024

Lineage tracing of Shh+ floor plate cells and dynamics of dorsal-ventral gene expression in the regenerating axolotl spinal cord

Both development and regeneration depend on signalling centres, which are sources of locally secreted tissue-patterning molecules. As many signalling centres are decommissioned before the end of embryogenesis, a fundamental question is how signalling centres can be re-induced later in life to promote regeneration after injury. Here, we use the axolotl salamander model (Ambystoma mexicanum) to address how the floor plate is assembled for spinal cord regeneration. The floor plate is an archetypal vertebrate signalling centre that secretes Shh ligand and patterns neural progenitor cells during embryogenesis. Unlike mammals, axolotls continue to express floor plate genes (including Shh) and downstream dorsal-ventral patterning genes in their spinal cord throughout life, including at steady state. The parsimonious hypothesis that Shh+ cells give rise to functional floor plate cells for regeneration had not been tested. Using HCR in situ hybridisation and mathematical modelling, we first quantitated the behaviours of dorsal-ventral spinal cord domains, identifying significant increases in gene expression level and floor plate size during regeneration. Next, we established a transgenic axolotl to specifically label and fate map Shh+ cells in vivo. We found that labelled Shh+ cells gave rise to regeneration floor plate, and not to other neural progenitor domains, after tail amputation. Thus, despite changes in domain size and downstream patterning gene expression, Shh+ cells retain their floor plate identity during regeneration, acting as a stable cellular source for this regeneration signalling centre in the axolotl spinal cord.

developmental biology↗

bioRxiv2020

Modeling the spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

Axolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), characterized by a high-proliferation zone emerging 4 days post-amputation (Rost et al., 2016). What underlies this spatiotemporal pattern of cell proliferation, however, remained unknown. Here, we use modelling, tightly linked to experimental data, to demonstrate that this regenerative response is consistent with a signal that recruits ependymal cells during 85 hours after amputation within ~830{square}m of the injury. We adapted FUCCI technology to axolotls (AxFUCCI) to visualize cell cycles in vivo. AxFUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells. Our modeling and imaging move us closer to understanding bona fide spinal cord regeneration.

bioinformatics↗