Spinal cord regeneration progresses via developmental and non-developmental mechanisms in X. tropicalis

Abstract

Human spinal cord regeneration is hampered by the inability of resident neural stem cells to regenerate developmentally derived neuron diversity and organization after injury. Unlike humans, the Xenopus tropicalis spinal cord is capable of functional regeneration after amputation, although the regenerative extent and mechanisms driving neural diversity and patterning remain unknown. During my dissertation work, I investigated if the X. tropicalis spinal cord regenerates cell diversity and patterning via the same developmental mechanisms with which it was originally made. First, I showed that the spinal cord dorsal/ventral axis is re-established by Shh signaling after injury in a similar manner to embryogenesis (Angell Swearer, Perkowski, et al. 2025). Next, I found that spinal cord regeneration deploys cell-type-specific developmental and non-developmental strategies to restore neuron diversity, in a divergence from the traditional regenerative paradigm (Angell Swearer et al. 2025, preprint). Overall, these results indicate that successful regeneration recruits a dynamic combination of developmental and non-developmental signals to complete functional healing.