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.
