The problem of regeneration is fundamentally a problem of tissue homeostasis involving the replacement
of cells lost to normal ?wear and tear? (cell turnover), and/or injury. This attribute is of particular significance
to organisms possessing relatively long lifespans, as maintenance of all body parts and their functional
integration is essential for their survival. Because tissue replacement is broadly distributed among
multicellular life-forms, and the molecules and mechanisms controlling cellular differentiation are considered
ancient evolutionary inventions, it should be possible to gain key molecular insights about regenerative
processes through the study of simpler animals. We have chosen to study and develop the freshwater
planarian Schmidtea mediterranea as a model system because it is one of the simplest metazoans possessing
tissue homeostasis and regeneration, and because it has become relatively easy to molecularly manipulate
this organism. The developmental plasticity and longevity of S. mediterranea is in marked contrast to its
better-characterized invertebrate cohorts: the fruitfly Drosophila melanogaster and the roundworm Caenorhabditis
elegans, both of which have short lifespans and are poor at regenerating tissues. Therefore, planarians
present us with new, experimentally accessible contexts in which to study the molecular actions
guiding cell fate restriction, differentiation and patterning, each of which is crucial not only for regeneration
to occur, but also for the survival and perpetuation of all multicellular organisms.
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