Differential Regenerative Capacity of the Optic Tectum of Adult Medaka and Zebrafish

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.

Comparative Study in Zebrafish and Medaka Unravels the Mechanisms of Tissue Regeneration

“…A comparative study of brain regeneration in medaka and zebrafish has also been reported very recently (Shimizu and Kawasaki, 2021). Medaka shares a similar brain structure with zebrafish and neural stem cells (NSCs) niche for brain development and growth (Adolf et al, 2006;Grandel et al, 2006;Alunni et al, 2010;Kuroyanagi et al, 2010).…”

“…Main NSCs exist in the optic tectum of both zebrafish and medaka, including the proliferative neuroepithelial-like stem (NE) cells and the quiescent RG cells (Alunni et al, 2010;Ito et al, 2010;Takeuchi and Okubo, 2013;Dambroise et al, 2017). However, medaka could not regenerate their optic tectum after stab injury and thus leaving a permanent scar (Shimizu and Kawasaki, 2021). In medaka, RG cells were similarly activated for proliferation upon tectum injury, but they failed to differentiate into neuron cells.…”

“…Heart (Ito et al, 2014;Lai et al, 2017) Retina (Lust and Wittbrodt, 2018) Brain (optic tectum) (Shimizu and Kawasaki, 2021) Caudal Fin (Katogi et al, 2004) Kidney (Watanabe et al, 2009) Liver (Van Wettere et al, 2013) Pancreas (Otsuka and Takeda, 2017) Notochord (Seleit et al, 2020) Lateral Line (Seleit et al, 2017b) Posterior lateral line (pLL) nerve (Seleit et al, 2022) Gill (Stolper et al, 2019) African Killifish (Nothobranchius furzeri)…”

“…Are there tissue-specific contributions/responses, for example, residential immune cells, tissue-specific injury response elements, or even changes in the epigenomic landscape? These questions may be best addressed in medaka where the organ-specific regenerative capacities are uneven and well studied, including the regenerative fin (Katogi et al, 2004), kidney (Watanabe et al, 2009), liver (Van Wettere et al, 2013), and pancreas (Otsuka and Takeda, 2017), and non-regenerative heart (Ito et al, 2014;Lai et al, 2017), retina (Lust and Wittbrodt, 2018), and brain (Shimizu and Kawasaki, 2021). The potential findings can be cross-species compared and further validated in zebrafish loss-of-function and medaka gainof-function experiments.…”

“…In addition, zebrafish shares more than 70% of homologous genes with humans, and conserved signaling pathways and metabolic networks, making it a valuable model for biomedical research (Howe et al, 2013). Interestingly, medaka possesses regenerative capacity in fin (Katogi et al, 2004), kidney (Watanabe et al, 2009), liver (Van Wettere et al, 2013), pancreas (Otsuka and Takeda, 2017), lateral line neuromasts (Seleit et al, 2017b), and gills (Stolper et al, 2019) but is impaired to regenerate the heart (Ito et al, 2014;Lai et al, 2017), retina (Lust and Wittbrodt, 2018), brain (Shimizu and Kawasaki, 2021), and posterior lateral line (pLL) nerve cells (Seleit et al, 2022). This uneven regenerative capacity across organs is in sharp contrast with zebrafish, which can regenerate almost all organs, including the heart (Poss et al, 2002), retina (Vihtelic and Hyde, 2000;Sherpa et al, 2008), brain (Kroehne et al, 2011;Marz et al, 2011;Kishimoto et al, 2012), spinal cord (Becker et al, 1997;Ghosh and Hui, 2018), notochord (Garcia et al, 2017;Lopez-Baez et al, 2018), fin (Poss et al, 2003), kidney (Diep et al, 2011), liver (Sadler et al, 2007), pancreas (Moss et al, 2009), gills (Mierzwa et al, 2020), and lateral line (Hair cells) (Lush and Piotrowski, 2014;Cruz et al, 2015).…”