Vertebrates show conserved left-right (L-R) asymmetry of internal organs controlled by Nodal-Pitx2/Lefty signaling [1][2][3]. Modifications in L-R asymmetry occur in mutants [4] and rarely in humans [5], but little is known about natural L-R changes during evolution. Here we describe changes in L-R asymmetry in Astyanax mexicanus, a teleost with ancestral surface (surface fish) and derived cave (cavefish) morphs [6]. In teleosts, Nodal-Pitx2 signaling is activated in the left lateral plate mesoderm (LPM), the cardiac tube jogs to the left and loops to the right (D-looping), and the liver and pancreas form on opposite sides of the midline. Surface fish show conventional L-R patterning, but cavefish can show Nodal-Pitx2 expression in the right LPM or bilaterally, left (L)-looping hearts, and reversed liver and pancreas asymmetry, and these reversals have no effect on survival. The Lefty1 Nodal antagonist is expressed along the surface fish and cavefish midlines, but expression of the Lefty2 antagonist is absent in the LPM of most cavefish embryos, suggesting a role for lefty2 (lft2) in changing organ asymmetry. Although CRISPR-Cas9 lft2 editing affected D-looping in surface fish, the cavefish lft2 gene showed no coding mutations, and was expressed normally during cavefish gastrulation, suggesting downregulation by regulatory changes. Reciprocal hybridization, the fertilization of cavefish eggs with surface fish sperm and vice versa, indicated that the change in cavefish L-R asymmetry is a maternal genetic effect. Our studies reveal natural changes in internal organ asymmetry during evolution and introduce A. mexicanus as a new model to study the underlying mechanisms.
The teleost Astyanax mexicanus is a single species with surface dwelling (surface fish) and cave dwelling (cavefish) morphs. Constructive and regressive traits have evolved in cavefish as adaptations for survival in perpetual darkness. In addition to darkness, cavefish must cope with de-oxygenated aquatic environments. Blood cell quantification and expression of hematopoietic marker genes indicated that cavefish have more erythrocytes than surface fish, and that this increase has a developmental basis. In contrast to zebrafish and other teleost embryos, in which erythrocyte formation is restricted to the posterior lateral mesoderm, the anterior as well as the posterior lateral mesoderm is involved in red blood cell formation in Astyanax embryos, and both of these hematopoietic domains are expanded in cavefish embryos. Erythroid development in the anterior mesoderm may be a pre-adaptation for surface fish to successfully colonize hypoxic cave environments. We also show that cavefish are less sensitive to phenylhydrazine-induced erythrocyte ablation than surface fish, suggesting a functional advantage of increased red blood cells. By mimicking a hypoxic cave environment in the laboratory, we further demonstrate that cavefish respond to hypoxia differently than surface fish. Surface fish with fewer red blood cells use overall metabolic depression to counteract hypoxia, whereas cavefish with larger numbers of erythrocytes respond to hypoxia by switching to anaerobic metabolism. These results suggest that cavefish may have adapted to hypoxic environments by enhancing the capacity to form erythrocytes and reprogramming metabolism. Summary Astyanax mexicanus cavefish adapt to life in hypoxic cave environments by evolving the capacity to increase red blood cell numbers during early development and reprogramming metabolism to favor anaerobic processes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.