THE ROLE OF CONNEXINS IN THE INJURY INDUCED REACTIVATION OF ENDOGENOUS SPINAL PROGENITORS

Ependymal cells (ECs) of the mammalian spinal cord form a latent stem cell niche that becomes reactivated after spinal cord injury (SCI), yet this response does not lead to functional regeneration. In the adult mouse, ECs behave largely as isolated units whereas injury induces the functional coupling via gap-junctions and the resumption of proliferation, suggesting a key role for connexin (Cx) signaling in niche re-activation. Using inducible, EC-specific genetic ablation of Cx26 or Cx43 in mice, we show that deletion of either Cx reduces EC proliferation hampering glial scar formation. Notably, loss of Cx43 results in a marked downregulation of Cx26, indicating that Cx26 acts as a critical downstream component of Cx43-dependent early signaling after SCI.
To examine Cx regulation in a regenerative context, we investigated SCI in Trachemys scripta elegans, an amniote capable of spinal cord reconnection and functional recovery. Time-resolved bulk RNA-seq analysis of the injured cord revealed stable expression of Cx26 and Cx43 in sham-operated animals and at 1 day post-lesion. In contrast, Cx43 was strongly upregulated from 4 to 15 days post-injury while Cx26 displayed a transient induction at 7 days post-injury, suggesting a temporally coordinated regulation of Cxs during repair.
Ongoing single-nucleus RNA-seq analyses are resolving the cellular sources of these transcriptional changes. Together, our findings identify Cx26 as a key regulator of EC activation in non-regenerative mammals and reveal temporally structured Cx regulation in a regenerative vertebrate, providing a comparative framework to identify mechanisms that may enhance spinal cord repair.