Cavefish cope with environmental hypoxia by developing more erythrocytes and overexpression of hypoxia inducible genes

  1. Corine M van der Weele
  2. William R Jeffery  Is a corresponding author
  1. University of Maryland, United States


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 1 (hif1) pathway genes, and some hif1 genes are constitutively upregulated in normoxic cavefish to similar levels as in hypoxic surface fish. We conclude that cavefish cope with hypoxia by increasing erythrocyte development and constitutive hif1 gene overexpression.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting file. Source data files have been provided for Figures 1, 2, 4, 5, 6 and 7

Article and author information

Author details

  1. Corine M van der Weele

    Department of Biology, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. William R Jeffery

    Department of Biology, University of Maryland, College Park, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6997-2946


National Institutes of Health (EY024941)

  • William R Jeffery

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals. All of the animals were maintained and handled according to Institutional Animal Care guidelines of the University of Maryland, College Park (IACUC #R-NOV-18-59) (Project 1241065-1). All surgery was performed under anesthesia and every effort was made to minimize suffering.

Reviewing Editor

  1. Nicolas Rohner, Stowers Institute for Medical Research, United States

Publication history

  1. Preprint posted: December 13, 2019 (view preprint)
  2. Received: April 5, 2021
  3. Accepted: December 31, 2021
  4. Accepted Manuscript published: January 5, 2022 (version 1)
  5. Version of Record published: January 18, 2022 (version 2)


© 2022, van der Weele & Jeffery

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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  1. Corine M van der Weele
  2. William R Jeffery
Cavefish cope with environmental hypoxia by developing more erythrocytes and overexpression of hypoxia inducible genes
eLife 11:e69109.

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