Abstract

Spinal cord regeneration in Xenopus Juan Larraín, PhD Center for Aging and Regeneration Millennium Nucleus for Regenerative Biology P. Universidad Católica de Chile

Amphibians, such as adult urodeles (e.g. newts) and anuran larvae (e.g. Xenopus) are able to regenerate the spinal cord after injury. In the case of Xenopus tadpoles this capacity is lost during metamorphosis. We are studying the cellular and molecular mechanism that allow this regenerative process and why is lost during metamorphosis. In particular, we have focused in the role of neural stem (NSC) and progenitor cells (NPC) in spinal cord regeneration in Xenopus tadpoles using two experimental approaches: tail amputation and spinal cord transection. Spinal cord injury (SCI) in Xenopus tadpoles results in a global increase of Sox2 and nestin levels and activation of Sox2+ cells measured by BrdU labeling experiments. Experimental reduction of Sox2 activity diminished proliferation of spinal cord resident cells affecting spinal cord regeneration after tail amputation. Interestingly, reduction of Sox2 levels also affects tail regeneration suggesting that spinal cord regeneration commands the whole regenerative process. The levels of Sox2+ cells levels correlate with regenerative capabilities during metamorphosis suggesting that activation of this cells is required for spinal cord regeneration. In addition, Sox2+ cell aggregates repopulated the ablation gap in the spinal cord transection model giving further support to its role in spinal cord regeneration. In summary, we have established that SCI in Xenopus tadpoles results in activation of Sox2+ cells making it an excellent model system to study the biology of NSC and/or NPC and its role in spinal cord regeneration. Currently we are working on the following research lines: i) To identify and characterize bona fide NSC and NPC resident in the spinal cord; ii) To study and compare the activation and fate of Sox2+ cells in regenerative and non-regenerative stages along the process of metamorphosis; iii) to evaluate if SCI results in glial scar formation; iv) To perform a high-through put analysis to compare the transcriptome activated in response to SCI in different stages.