Purpose: The aim of the study was to investigate the functional role of L1.2, the zebrafish paralog of L1.1 and ortholog of mammalian L1CAM in adult zebrafish spinal cord regeneration after injury. L1CAM and L1.1 have shown beneficial features in ameliorating nervous system dysfunctions in different experimental paradigms. It thus deemed important to characterize the L1.2 member of the L1CAM family, the functions of which are unknown.
Methods: Spinal cord transection of adult zebrafish, application of anti-sense morpholino to reduce L1.2 expression, qPCR, immunohistology, immunoblotting, in situ hybridization, retrograde tracing, anterograde tracing.
Results: Similar to L1.1, L1.2 expression in adult zebrafish is upregulated after spinal cord transection. By co-localization of in situ hybridization and immunohistology, L1.2 is expressed in neurons and, in contrast to L1.1, it is also expressed in GFAP-immunoreactive glia. Reducing L1.2 protein levels leads to impaired locomotor recovery and reduction of regrowth of severed descending axons from a brain stem nucleus which is composed of neurons innately capable of axonal regrowth.
Conclusions: Our findings support the speculation that paralogs of duplicated genes can exert similar functions and may thus represent an advantage over other species that do not carry duplicated genes.
Keywords: Adhesion molecule L1; Danio rerio; morpholino; regeneration; spinal cord injury.