Changing landscapes: uncovering the molecular mechanisms of spinal cord development and regeneration in the axolotl

Axolotls have the remarkable capacity to regenerate the spinal cord. This ability relies on resident spinal cord stem cells. Following injury, these cells self-renew extensively and give rise to all cell types of the regenerated spinal cord. This contrasts with their mouse and human counterparts, which display very limited potency in the injured spinal cord. The axolotl thus represents a unique system to explore how resident stem cells transform into a highly regenerative cell state.

In previous work, we discovered that regenerating spinal cord stem cells in the axolotl redeploy a gene expression programme that resembles that of cells that build the spinal cord during embryonic development. However, how this gene expression programme becomes inactive when development is complete, and how it is reactivated upon injury remains unknown. We hypothesise that changes in the genomic accessibility landscape will allow us to uncover how these processes are orchestrated.

The availability of axolotl genome information and genome editing tools make it now possible to tackle these questions with unprecedented detail in axolotls and gain new insights into the fundamental mechanisms of regeneration. In this interdisciplinary project, the student will:

1. Characterise the expression of key transcription factors and signalling molecules during spinal cord development and regeneration with expert guidance from Prof Val Wilson (2nd supervisor).

2. Analyse the genomic landscape of spinal cord stem cells during development and regeneration with expert support from Dr Vicki Metzis (3rd supervisor).

3. Test the role of key transcription factors in the reactivation of the regeneration programme using CRISPR technology.