Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK
Madeleine E. Lemieux
Bioinfo, Plantagenet, ON K0B 1L0, Canada
Abigail C. Killen
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK
Juanjuan Zhao
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK
Zhilian Hu
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK
Joey Riepsaame
Genome Engineering Oxford, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
Noémie Hamilton
Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, UK
Tetsuhiro Kudoh
Biosciences, College of Life and Environmental Sciences, Geoffrey Pope Building, University of Exeter, Stocker Road, Exeter, EX4 4QD, UK
Paul R. Riley
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK
Ronny van Aerle
Centre for Environment, Fisheries and Aquaculture Science (Cefas), Weymouth, Dorset DT4 8UB, UK
Yoshiyuki Yamamoto
Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, UK; Corresponding author
Mathilda T.M. Mommersteeg
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK; Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, UK; Corresponding author
Summary: Although Astyanax mexicanus surface fish regenerate their hearts after injury, their Pachón cave-dwelling counterparts cannot and, instead, form a permanent fibrotic scar, similar to the human heart. Myocardial proliferation peaks at similar levels in both surface fish and Pachón 1 week after injury. However, in Pachón, this peak coincides with a strong scarring and immune response, and ultimately, cavefish cardiomyocytes fail to replace the scar. We identified lrrc10 to be upregulated in surface fish compared with Pachón after injury. Similar to cavefish, knockout of lrrc10 in zebrafish impairs heart regeneration without affecting wound cardiomyocyte proliferation. Furthermore, using quantitative trait locus (QTL) analysis, we have linked the degree of heart regeneration to three loci in the genome, identifying candidate genes fundamental to the difference between scarring and regeneration. Our study provides evidence that successful heart regeneration entails a delicate interplay between cardiomyocyte proliferation and scarring. : Stockdale et al. identify the Mexican cavefish as a model for heart regeneration research. This model provides an opportunity for direct comparison of natural regeneration versus scarring within a single species. Furthermore, they have identified key genomic regions regulating heart regeneration using an unbiased quantitative trait loci analysis approach. Keywords: Mexican cavefish, heart regeneration, fibrotic scar, QTL, myocardial proliferation, lrrc10
