Cavefish Increase Red Blood Cell Development and Reprogram Metabolism as Adaptations to Environmental Hypoxia

Abstract

Dark caves lacking primary productivity can expose subterranean animals to hypoxia. We used the surface-dwelling (surface fish) and cave-dwelling (cavefish) morphs of Astyanax mexicanus as a model for understanding the mechanisms of hypoxia tolerance in the cave environment. Primitive hematopoiesis, which is restricted to the posterior lateral mesoderm in other teleosts, also occurs in the anterior lateral mesoderm in Astyanax, potentially pre-adapting surface fish for hypoxic cave colonization. Cavefish have enlarged both hematopoietic domains and develop more erythrocytes than surface fish, which are required for normal development in both morphs. Laboratory induced hypoxia suppresses growth in surface fish but not in cavefish. Both morphs respond to hypoxia by overexpressing Hypoxia-Inducible Factor (HIF) pathway genes, but some hif genes are constitutively upregulated in normoxic cavefish to similar levels as hypoxic surface fish. We conclude that cavefish cope with hypoxia by increasing erythrocyte development and constitutive HIF gene overexpression. SummaryAstyanax mexicanus cavefish cope with hypoxic environments by expanding embryonic hematopoietic domains, increasing the capacity for erythrocyte development, and constitutive overexpression of hypoxia-inducible genes.