Although Astyanax mexicanus surface fish regenerate
their hearts after injury, their Pacho´ n cavedwelling
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 Pacho´ n 1 week after injury.
However, in Pacho´ n, 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 Pacho´ n 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.