Investigating the Role of Meteorin and Meteorin-like During Spinal Cord Development and Regeneration in Zebrafish

Radial glia are the primary neural stem cells during embryonic development, giving rise to both neurons and glia, and serving as scaffolds for migrating progenitor cells and axons during neurogenesis and commissure formation. Previous work in the Barresi Lab has shown that radial glia are essential for central nervous system (CNS) development in zebrafish and are regulated by a variety of signaling pathways. We have focused on the putative secreted proteins Meteorin (metrn) and Meteorin-like (metrnl) as potential regulators of radial glia during development. Given the critical role radial glia also play in regeneration, we investigated whether metrn and metrnl respond to spinal cord injury and contribute to regenerative processes. This study characterized metrn and metrnl expression during larval spinal cord development and regeneration, and examined their regulation by the Hedgehog signaling pathway. We found that both genes are expressed in the spinal cord and developing muscle, with metrn enriched in the ventricular zone and metrnl more restricted to the floor plate. Cyclopamine treatment resulted in decreased expression of both genes, supporting the idea that they act downstream of Hedgehog signaling. Following spinal cord injury, both metrn and metrnl were upregulated at the injury site. Metrn showed sustained expression during glial bridging, while metrnl peaked earlier, possibly reflecting roles in immune response or muscle repair. These findings suggest that metrn and metrnl are novel, potentially Hedgehog-responsive factors involved in both spinal cord development and regeneration.