B02: Pre and post metamorphosis spinal cord regeneration in frogs

Frogs may regenerate CNS neurons before but not after metamorphosis. While some differences in the biochemical landscape of injured frog tissue before and after metamorphosis have already been identified, they cannot fully explain the tremendous differences in the regenerative capacity of neurons, suggesting that other signals may contribute to regulating wound healing and neuronal regeneration. B02 will study mechanical, cellular and molecular changes of spinal cord tissue in the African clawed frog Xenopus laevis before and after metamorphosis and determine which combination of parameters are responsible for the loss of neuronal regeneration in post-metamorphotic froglets.  Tissue mechanics will be assessed by atomic force microscopy and Brillouin microscopy, differences in the genetic and chemical state of cells and the extracellular matrix will be measured using single cell RNAseq, HCR, immunohistochemistry, and proteomics. We will perturb tissue mechanics and gene expression of identified candidate genes in the post metamorphosis spinal cord to ultimately facilitate neuronal regeneration in the adult spinal cord, which would normally fail. Within the timeframe of this 4-years project, we aim to characterise the mechanical landscape of the Xenopus spinal cord before and after injury in regenerative and non-regenerative stages.  We will compare the results with published data on non-regenerative mammalian spinal cords and regenerative zebrafish spinal cords and test if manipulating spinal cord mechanics in non-regenerative, postmitotic froglets rescues neuronal regeneration. The findings of this study will generate important data justifying in vivo approaches. Data acquired here will be of great importance to projects B01 and X01, the method applied here will be extensively used in many other B projects. Spinal cord mechanics could, in addition to well-established genetic and chemical signaling, play a major role in regulating regeneration. Identifying cellular and extracellular components critical for tissue stiffness and neuronal regeneration may reveal conserved signaling pathways. If re-establishing regenerative spinal cord mechanics in non-regenerative froglets in vivo facilitates neuronal regeneration, this project may lead to a much better understanding of spinal cord injuries. It is intriguing to speculate if our findings in Xenopus can be translated into human physiology and contribute to novel treatment approaches in clinical practice.

Project leader: Prof. Dr. Kristian Franze

Positions: 1 doctoral researcher