Abstract
Tissue regeneration has been in the spotlight of research for its fascinating nature and potential applications in human diseases. The trait of regenerative capacity occurs diversely across species and tissue contexts, while it seems to decline over evolution. Organisms with variable regenerative capacity are usually distinct in phylogeny, anatomy, and physiology. This phenomenon hinders the feasibility of studying tissue regeneration by directly comparing regenerative with non-regenerative animals, such as zebrafish (Danio rerio) and mice (Mus musculus). Medaka (Oryzias latipes) is a fish model with a complete reference genome and shares a common ancestor with zebrafish approximately 110–200 million years ago (compared to 650 million years with mice). Medaka shares similar features with zebrafish, including size, diet, organ system, gross anatomy, and living environment. However, while zebrafish regenerate almost every organ upon experimental injury, medaka shows uneven regenerative capacity. Their common and distinct biological features make them a unique platform for reciprocal analyses to understand the mechanisms of tissue regeneration. Here we summarize current knowledge about tissue regeneration in these fish models in terms of injured tissues, repairing mechanisms, available materials, and established technologies. We further highlight the concept of inter-species and inter-organ comparisons, which may reveal mechanistic insights and hint at therapeutic strategies for human diseases.
Highlights
TISSUE REGENERATION IN MODEL ORGANISMSReparative regeneration refers to replacing damaged or lost body parts with new tissue, an injury response that restores the tissue homeostasis and function in the optimal scenario (Iismaa et al, 2018)
Taking the heart for example, most cardiomyocytes stop proliferating soon after birth, and there is no stem-like or progenitor cell population identified in the adult hearts (Bely and Nyberg, 2010; Steinhauser and Lee, 2011; Mollova et al, 2013; Bergmann et al, 2015)
In a loss-of-function setting, delayed macrophage recruitment by clodronate liposome pre-depletion abolished the regenerative capacity in zebrafish (Lai et al, 2017), which correspond nicely with findings in neonatal mice (Aurora et al, 2014)
Summary
Reparative regeneration refers to replacing damaged or lost body parts with new tissue, an injury response that restores the tissue homeostasis and function in the optimal scenario (Iismaa et al, 2018). In a loss-of-function setting, delayed macrophage recruitment by clodronate liposome pre-depletion abolished the regenerative capacity in zebrafish (Lai et al, 2017), which correspond nicely with findings in neonatal mice (Aurora et al, 2014) These results support an essential role of macrophage function in heart regeneration across species and encore the requirement of the macrophage function in the regeneration of other organs, including fin, retina, optic tectum, brain, and spinal cord reviewed elsewhere (Var and Byrd-Jacobs, 2020). One may wonder whether systemic inflammation and immune response contribute differently upon fin and heart injury in medaka, which will be further discussed and await future investigation Overall, all these studies highlight the strength of interspecies comparisons between zebrafish (regenerative) and medaka (non-regenerative) organs to identify (and in some cases to validate) the potential triggers of tissue regeneration. This type of study paved the way for identifying evolutionarily conserved RREs, which can be analyzed in medaka to decipher how these RREs exist and regulate the regenerative programs in a tissue-specific manner
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