Abstract
Zebrafish have superior regenerative capacity in the central nervous system (CNS) compared to mammals. In contrast, medaka were shown to have low regenerative capacity in the adult heart and larval retina, despite the well-documented high tissue regenerative ability of teleosts. Nevertheless, medaka and zebrafish share similar brain structures and biological features to those of mammals. Hence, this study aimed to compare the neural stem cell (NSC) responses and regenerative capacity in the optic tectum of adult medaka and zebrafish after stab wound injury. Limited neuronal differentiation was observed in the injured medaka, though the proliferation of radial glia (RG) was induced in response to tectum injury. Moreover, the expression of the pro-regenerative transcriptional factors ascl1a and oct4 was not enhanced in the injured medaka, unlike in zebrafish, whereas expression of sox2 and stat3 was upregulated in both fish models. Of note, glial scar-like structures composed of GFAP+ radial fibers were observed in the injured area of medaka at 14 days post injury (dpi). Altogether, these findings suggest that the adult medaka brain has low regenerative capacity with limited neuronal generation and scar formation. Hence, medaka represent an attractive model for investigating and evaluating critical factors for brain regeneration.
Highlights
Zebrafish have a superior ability to regenerate various tissues, including the central nervous system (CNS) and heart, compared with mammals (Becker et al, 1997; Poss et al, 2002; Raymond et al, 2006; März et al, 2011)
To examine that this regenerative mechanism was present in medaka, stab wound injury was induced in the right hemisphere of the optic tectum of medaka and radial glia (RG) proliferation was quantified by counting brain lipid binding protein (BLBP) (RG marker), and proliferating cell nuclear antigen (PCNA) doublepositive cells
Additional analysis between 6 h post injury to 7 dpi (Figures 1C–F) further revealed that the number of proliferative RG significantly increased from 1 dpi and peaking at around 2 dpi, with no significant difference being observed at 7 dpi (Figure 1G), which follows the same response trend observed in the injured zebrafish (Shimizu et al, 2018; Yu and He, 2019)
Summary
Zebrafish have a superior ability to regenerate various tissues, including the central nervous system (CNS) and heart, compared with mammals (Becker et al, 1997; Poss et al, 2002; Raymond et al, 2006; März et al, 2011). To better understand the molecular mechanisms underlying the high regenerative capacity of zebrafish, comparative analyses of tissue regeneration in the retina and heart between zebrafish and mice have been performed, given their similarities in cell type and tissue structure (Kang et al, 2016; Hoang et al, 2020; Simões et al, 2020). Comparative studies using next-generation sequencing technology have revealed differences in the immune response or expression of transcriptional factors associated with tissue regeneration (Hoang et al, 2020; Simões et al, 2020). The brain structure and cell types between zebrafish and mice are quite different To investigate the mechanisms that contribute to the high regenerative capacity of the zebrafish brain, non-regenerative animal models with similar brain structures and biological features are warranted
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