The singular regenerative abilities of planarians require a population of stem cells known
as neoblasts. In response to wounding, or during the course of cell turnover, neoblasts are signaled to divide and/or
differentiate,thereby replacing lost cell types. The study of these pluripotent stem cells and their role in planarian
regeneration has been severely hampered by the reported inability of planarians to incorporate exogenous DNA precursors;
thus, very little is known about the mechanisms that control proliferation and differentiation of this stem cell population
within the planarian. Here we show that planarians are, in fact, capable of incorporating the thymidineanalogue bromodeoxyuridine
(BrdU), allowing neoblasts to be labeled specifically during the S phase of the cell cycle. We have used BrdU labeling to
study the distribution of neoblasts in the intact animal, as well as to directly demonstrate the migration and differentiation
of neoblasts. We have examined the proposal that a subset of neoblasts is arrested in the G2 phase of the cell cycle by
double-labeling with BrdU and a mitosis-specific marker; we find that the median length of G2 (~6 h) is sufficient to
account for the initial mitotic burst observed after feeding or amputation. Continuous BrdU-labeling experiments also
suggest that there is not a large, slow-cycling population of neoblasts in the intact animal. The ability to label specifically
the regenerative stem cells, combined with the recently described use of double-stranded RNA to inhibit gene expression in
the planarian, should serve to reignite interest in the flatworm as an experimental model for studying the problems of metazoan
regeneration and the control of stem cell proliferation.
|