Genetic approaches to organ regeneration in zebrafish.
Development of therapies that stimulate the regenerative
capacity of human organs would represent a medical
panacea. By contrast with mammals, salamanders and
common aquarium fish have a tremendous capacity for
regeneration. Thus, we have a lot to learn from lower
vertebrate creatures. Surprisingly, little is known
about the molecules that stimulate and maintain regeneration,
and even the cellular events that define regeneration
are poorly understood. Through use of the popular
laboratory model system, zebrafish, we can apply molecular
genetic tools to dissect regeneration.
Recently, we found that mutants that fail to regenerate
amputated fins can be identified, and the responsible
mutations can be positionally cloned. Also, we found
that zebrafish possess a striking ability to renew
surgically removed heart muscle. We are currently
following up on these discoveries in two ways. First,
by candidate gene testing, we are examining the potential
roles of common embryonic signaling pathways in the
initiation of fin and heart regeneration. Second,
we are refining methods to perform mutagenesis screens
for additional regeneration-defective mutants. Ultimately,
we hope that by determining the mechanisms responsible
for organ regeneration in zebrafish, we can 1) define
factors that distinguish regenerating from non-regenerating
systems, and 2) assess whether regeneration can be
enhanced in injured mammalian organs.
