Genetic treasures: blind cavefish who traded eyes for super powered noses

by Vaiva M. Palunas, Scripps College [edited by Lars Schmitz as part of BIOL 167 “Sensory Evolution”, an upper division class at the W.M. Keck Science Department. Written for educational purposes only].

Cave inhabitants, or troglobites, often look very different from their surface dwelling counterparts or even those animals that spend just some of their time underground in the dark. Cave habitats support little life, yet some animals live just fine never seeing the sun, swimming in the eternal darkness of underground lakes and rivers. Often pale, eyeless, and slow moving, many cave species look eerily similar as they coast around in the pitch-black. The morphological continuity of cave species has puzzled scientists for years, but the discovery of a certain species of cavefish in Mexico has provided a genetic key to figuring out what may explain this intriguing pattern. They’re called Astyanax mexicanus, and they’re special because they are relative newcomers to the caves (Figure 1, Krishnan and Rohner, 2016). They appear white, are eyeless and are fully adapted to life in the dark, but they are still genetically similar enough to their surface dwelling relatives that they can interbreed and produce viable offspring.


Figure 1 (Fig. 1 from Krishnan, J., & Rohner, N., 2016).  Images of (c) surface and (d) cave morphs of Astyanax mexicanus from three different caves and their respective habitats of (a) streams and (b) cave systems.

This suit of characteristics is invaluable to geneticists, because it allows them to pinpoint what genes are involved in traits like eye loss in the fish. A. mexicanus has become a popular model organism for genetic studies on both development and evolution because of their unique traits and genetic malleability (Casane and Rétaux, 2016). When studying cavefish, one question that arises immediately is how they survive without eyes. Most animals we are familiar with use their eyes and sense of sight to find food, mates, and sample their surroundings for dangers, among other things. However, in complete darkness light-dependent eyes are not useful at all. It is apparent that cavefish are still able to survive and reproduce without sight, so the question for research becomes finding out what ultimately caused cavefish to lose their eyes? Was it the evolutionary push to lose eyes simply to save energy, or to make room for other, supercharged, senses that do work in the dark?

Hélène Hinaux and colleagues sought to answer this question, specifically, whether our friend Astyanax mexicanus trades its eyes for a better nose by diverting metabolic energy from eye development into olfactory organs and brain tissue. The research team investigated the development of eyes and olfactory organs in cave and surface fish embryos by looking at several pathways known to be instrumental in the development of the head. These pathways consist of developmental processes linked to a specific chemical receptor or messenger molecule that are often conserved over evolutionary time and therefore popular targets for study. The specific pathways were Sonic hedgehog (Shh), Fibroblast growth factor 8 (FgF8), and Bone morphogenetic protein 4 (Bmp4), all of which are conserved through evolution and therefore play essential roles in development of various parts of the vertebrate head region.

By looking at images of developing fish embryos that had been subjected to several genetic treatments, Hinaux and colleagues discovered how these signaling pathways affect the development of both eyes and olfactory organs (Figure 2, Hinaux et al, 2016).

The development of eyes in cave and surface fish has been studied in depth and is relatively well understood; eyes in both fish morphs begin development the same way, but in cavefish, the cells making up the lens undergo apoptosis and die, initiating developmental differences (Figure 3; Krishnan and Rohner, 2016, Casane and Rétaux, 2016). Before this paper was published, we knew that the regression of eyes in A. mexicanus was caused by evolutionary selective pressures of the cave environment, and was related to the Shh pathway; we also knew that this regression was likely linked to some kind of sensory system trade-off (Yoshizawa et al, 2012).

The actual existence and exact timing of the sensory trade-off event (lens apoptosis), roughly 24 hours after fertilization during the neural plate stage of the fish embryos, was unknown until Hinaux and colleagues published their study (Hinaux et al, 2016). Hinaux and colleagues also further elucidated the mechanisms causing eye-nose trade-off in development of cavefish, by looking at multiple developmental pathways.


Figure 2 (panels F and G from Fig. 5 of Hinaux, et al., 2016).  (F) A schematic showing effects of Shh, Fgf8, and Bmp4 signally pathways on the lens and olfactory placodes. (G) Brain placodes (relevant areas of the brain at a set level of development) shown in place in the head, nose at top, with effects of Shh, Fgf8, and Bmp4.  Arrows show activation, flat ends show inhibition.

Along with arresting development of the lens and other parts of the eye, cavefish were found to have larger olfactory placodes in their brains and correspondingly larger olfactory organs as they developed when compared to surface fish (Hinaux et al, 2016). This was an exciting discovery because it showed a relatively late determination of brain tissue in developing fish. The olfactory system of cavefish benefits from the loss of eyes, as all three of the pathways studied promote growth of the olfactory placode while leading to the reduction of the lens placode: Fgf8 through heterochrony, Shh through hyper-signaling, and Bmp4 through its absence in the anterior portion of the head, leading to lens placode inactivation (Figure 2, Hinaux et al, 2016). It seems the answer to our earlier question is that the need for a larger and more developed nose pushed energy and resources away from the developing eye towards the nose and its associated brain tissue.


Figure 3 (Fig. 2 from Krishnan and Rohner, 2016).  Side by side schematic of eye development in cave and surface fish.  Areas affected by Shh shown in blue.  Lens apoptosis in cavefish leads to eyeless adults.

After finding this exciting sensory trade-off in development, Hinaux and colleagues tested the olfactory capabilities of cavefish to compare chemical sensitivity between cave and surface fish. By exposing fish to increasingly smaller concentrations of amino acids, specifically alanine and serine, the researchers found the lower limit of the fish’s sense of smell. Their results were astounding; cavefish not only showed much higher olfactory sensitivity than surface fish of the same species, but even gave sharks a run for their money. Cavefish can detect levels of alanine in the water at concentrations as low as 10-10 M (3.36×10-8 grams/gallon) (Figure 4, Hinaux et al, 2016), which is 5 orders of magnitude better than the surface dwellers..


Figure 4 (Fig. 8 from Hinaux et al., 2016).  Graphs showing olfactory response and lower limits of cave (CF) and surface (SF) morphs.  (A) and (B) shown side by side comparison of amino acid sensitivity of cave and surface fish, (C) shows lower limit for detection of alanine in cavefish. (D) Provides a summary of sensitivity for both morphs.

This supported the hypothesis that cavefish have a better nose than their surface counterparts, and suggests that by losing their eyes, cavefish could devote more energy to developing olfactory organs and tissues. It makes sense that cavefish would need a better sense of smell than surface fish. Any food that the cavefish could subsist on must wash in from outside the cave, since the lack of light in caves inhibits any sort of ecosystem based on photosynthesizing plants or plankton in the water (Casane and Rétaux, 2016). This makes the abundance of edible material in cave water very scarce; a supercharged nose would be extremely useful, and maybe even be essential, to cave living for A. mexicanus. The sensory shift from sight to smell in cavefish is a textbook example of sensory trade-off in the natural world, where shrinkage or complete removal of one sense allows for the betterment of another.

This paper falls into the field of EvoDevo—the fascinating overlap of developmental and evolutionary biology. The results above show how important and surprising this overlap can be. Studying the development of sensory organs in A. mexicanus gives us insight into not only the actual development of cavefish eyes, but also how the loss of eyes and the increased powers of olfaction evolved as the fish ventured into the darkness of caves. Minute changes in developmental signaling pathways must have occurred and proliferated, leading to the evolution of a new subset of the species. Continuing study on A. mexicanus is likely to reveal more interesting ideas on evolution and development, solely because of the possibilities this unique model animal gives us. A. mexicanus has many more secrets to reveal unrelated to its sensory systems; the existence of genetically related, yet geographically isolated, populations of fish present a veritable gold mine of scientific discovery on how one species becomes multiple in real evolutionary time. Stepping away from cavefish, this publication also opens the door to further research on other examples of sensory trade-off, in living species as well as those we learn about through the fossil record.



Casane, D., Rétaux, S. 2016 Evolutionary Genetics of the Cavefish Astyanax mexicanus. Advances in Genetics 95, 117–59. (DOI 10.1016/bs.adgen.2016.03.001)

Hinaux, H. et al. 2016 Sensory evolution in blind cavefish is driven by early embryonic events during gastrulation and neurulation. Development 143, 4521–4532. (DOI 10.1242/dev.141291)

Krishnan, J. & Rohner, N. 2016 Cavefish and the basis for eye loss. Phil. Trans. R. Soc. B 372, 20150487. (DOI 10.1098/rstb.2015.0487)

Yoshizawa, M., Yamamoto, Y., O’Quin, K. E. & Jeffery, W. R. 2012 Evolution of an adaptive behavior and its sensory receptors promotes eye regression in blind cavefish. BMC Biology 10, 108. (DOI 10.1186/1741-7007-10-108)

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