Unlike humans, some vertebrate animals are able to completely regenerate damaged appendages and other
organs. For example, adult zebrafish will regenerate the complex structure of an amputated caudalfintoa
degree that the original and replacementfins are indistinguishable. The blastema, a mass of cells that uniquely forms following appendage amputation in regenerating animals, is the major source of regenerated tissue.
However, the cell lineage(s) that contribute to the blastema and their ultimate contribution(s) to the regeneratedfin have not been definitively characterized. It has been suggested that cells near the amputation site
dedifferentiate forming multipotent progenitors that populate the blastema and then give rise to multiple
cell types of the regeneratedfin. Other studies propose that blastema cells are non-uniform populations
that remain restricted in their potential to contribute to different cell lineages. We tested these models by
using inducible Cre-lox technology to generate adult zebrafish with distinct, isolated groups of genetically labeled cells within the caudalfin. We then tracked populations of several cell types over the entire course of
fin regeneration in individual animals. We found no evidence for the existence of multipotent progenitors.
Instead, multiple cell types, including epidermal cells, intra-ray fibroblasts, and osteoblasts, contribute to
the newly regenerated tissue while remaining highly restricted with respect to their developmental identity.
Our studies further demonstrate that the regeneratingfin consists of many repeating blastema“units”dedicated to eachfin ray. These blastemas each have an organized structure of lineage restricted, dedifferentiated
cells that cooperate to regenerate the caudalfin.
© 2012 Elsevier Inc. All rights reserved