Subterranean Fishes of the World

5608

2022

AIM 2022

15

Provitamin A carotenoids and their metabolites (vitamin A, retinoic acid) regulate oxidative stress, gene expression, vision, and embryonic development. We found that Astyanax mexicanus Tinaja and Pachón cavefish have more carotenoids in adult tissues and the embryo yolk compared to surface fish fed the same laboratory diet. Carotenoid accumulation is not observed in Molino cavefish, indicating that it is not an obligatory consequence of eye loss. We found that genes important for carotenoid absorption and metabolism are differentially expressed in the guts of Tinaja cavefish and surface fish. Quantitative trait loci (QTL) mapping in surface/Pachón F2 hybrids linked carotenoid level with genetic changes in dtx2 E3 ubiquitin ligase. We hypothesize that mutations in dtx2 could alter Notch signaling in the gut, thereby by increasing absorptive cell number and enhancing carotenoid assimilation. Humans that eat a diet rich provitamin A carotenoids have reduced risk of developing obesity, diabetes, and tissue inflammation. Cavefish are hyperglycemic, insulin resistant, have fatty liver, and hypertrophic adipocytes, but do not exhibit signs of tissue inflammation (Rohner lab). In addition, traits that are modified in cavefish and show a maternal effect, like organ asymmetry (Jeffery lab) and hypothalamic neuron differentiation (Rétaux lab), are controlled by retinoic acid level in other species. We have developed carotenoid-variable diets to determine how altering carotenoid metabolites impacts adult and embryonic cavefish traits. Our study establishes A. mexicanus as a model to investigate the genetic basis of natural variation in provitamin A bioavailability and how it impacts disease-relevant physiology and nutritional control of embryonic development.

1