Subterranean Fishes of the World

6083

2023

bioRxiv preprint Februray 5, 2023

The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license

Physical injury and tissue damage is prevalent throughout the animal kingdom, with the ability to 49 quickly and efficiently regenerate providing a selective advantage. The skeletal muscle possesses 50 a uniquely large regenerative capacity within most vertebrates, and has thus become an important 51 model for investigating cellular processes underpinning tissue regeneration. Following damage, 52 the skeletal muscle mounts a complex regenerative cascade centered around dedicated muscle stem 53 cells termed satellite cells. In non-injured muscle, satellite cells remain in a quiescent state, 54 expressing the canonical marker Pax7 (Chen et al. 2020). However, following injury, satellite cells 55 exit quiescence, enter the cell cycle to initiate proliferation, asymmetrically divide, and in many 56 cases terminally differentiate into myoblasts, ultimately fusing with surrounding myoblasts and 57 pre-existing muscle fibers to resolve the regenerative process (Chen et al. 2020). The innate immune system, specifically those of the myeloid lineage, are crucial for the sequential 60 steps described above (Tidball et al. 2017). For example, within the first few hours of muscle 61 damage, neutrophils and macrophages infiltrate the damaged skeletal muscle to mediate the repair 62 process; including phagocytosis of cellular debris, secretion of cytokines regulating satellite cell 63 dynamics, and temporal control of the pro- and anti-inflammatory phases (Tidball et al. 2010). 64 However, investment into the innate immune system is energetically costly resulting in many 65 species decreasing investment in the innate immune system under nutrient-limited environments 66 (McDade et al. 2016). Whether this reduced investment into the innate immune system results in 67 a decreased capacity to mount a regenerative response following tissue damage remains unclear. 68 To this point, we utilized the emerging evolutionary model, Astyanax mexicanus, to investigate 69 the consequence of shifts in immune system investment on skeletal muscle regeneration.

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