L1.1 Is Involved in Spinal Cord Regeneration in Adult Zebrafish

Abstract

Adult zebrafish, in contrast to mammals, regrow axons descending from the brainstem after spinal cord transection. L1.1, a homolog of the mammalian recognition molecule L1, is upregulated by brainstem neurons during axon regrowth. However, its functional relevance for regeneration is unclear. Here, we show with a novel morpholino-based approach that reducing L1.1 protein expression leads to impaired locomotor recovery as well as reduced regrowth and synapse formation of axons of supraspinal origin after spinal cord transection. This indicates that L1.1 contributes to successful regrowth of axons from the brainstem and locomotor recovery after spinal cord transection in adult zebrafish.

Polysialyltransferase expression is linked to neuronal migration in the developing and adult zebrafish

“…Moreover, in contrast to mammals, adult zebrafish show significant levels of neurogenesis in almost all regions of the adult brain and have a pronounced capability to regenerate CNS lesions (Becker et al, 2004;Zupanc et al, 2005;Zupanc and Zupanc, 2006;Adolf et al, 2006;Grandel et al, 2006). For example, stab wounds in the adult zebrafish cerebellum are repaired within several days by an up-regulation of neurogenesis in the cerebellar molecular layer followed by directed migration of these neuronal progenitors toward the lesion site (Liu et al, 2004;Zupanc and Zupanc, 2006).…”

Function of Sox2 in ependymal cells of lesioned spinal cords in adult zebrafish

“…For SCI, fish were anesthetized by immersion in 0.033% ethyl 3-aminobenzoate methanesulfonic acid (MS-222; Sigma-Aldrich, MO, USA) in PBS for 5 min. A small incision was made at the side of the fish, and the spinal cord was completely transected 4 mm caudal to the brainstem-spinal cord junction using microscissors under visual control, followed by sealing of the wound using Histoacryl (B. Braun Melsungen AG, Melsungen, Germany) (Becker et al, 2004;Reimer et al, 2008). The fish were then reared in water at 28°C until appropriate time points.…”

Upregulation of anti-apoptotic factors in upper motor neurons after spinal cord injury in adult zebrafish

“…6). This three-dimensional behavior analysis revealed the recovery of motor function after SCI in more detail as compared to the previous study in which the two-dimensional tracking of fish was used (Becker et al, 2004). The biphasic pattern of behavioral recovery may be due to the increase in the number of GAP43 + descending axons.…”

“…Retrograde labeling of the NMLF and IMRF nuclei in the brainstem was performed by placing gelatin foam soaked with rhodamine dextran amine (RDA) or biocytin at the transection site in the spinal cord (Becker et al, 2004). In the area of NMLF (Fig.…”

“…In the rat model of spinal cord lesion, primary cortical motor neurons and motor neurons in the spinal cord become apoptotic and are lost within 1 week after spinal cord injury (SCI) (Hains et al, 2003). Conversely, zebrafish can regenerate axons of motor neurons and recover motor function 6-8 weeks after SCI (Van Raamsdonk et al, 1998;Becker et al, 2004). Similar to mammals, motor function in zebrafish is controlled by motor neurons from two distinct populations, the brainstem and the spinal cord.…”