Planarian Regeneration: Its End Is Its Beginning

In 1901, Thomas Hunt Morgan wrote: " The fact that the process of regener-ation is useful to the organism cannot be made to account for its existence in the organism " (Morgan, 1901). Although such words may strike us today as being counter to the general concepts of natural selection, Morgan reached this conclusion after an exhaustive study of regeneration in both plants and animals (Morgan, 1901). Morgan did, in fact, have a point. Take for example the nemer-tine worm Lineus ruber and its close relative Lineus viridis, species that are almost identical in morphological attributes and share similar if not identical environmental niches. Few would disagree that natural selection has played a key role in producing both extant forms. Harder to explain, however, is the fact that these two species, often found living in the same estuary, respond very differently to amputation. Amputate a part of L. ruber and the missing part regenerates ; amputate a part of L. viridis and no regeneration is observed (Brockes et al., 2001). In fact, multiple examples exist describing such intra-phyletic variability (Needham, 1952), as well as the most common and equally puzzling distribution of regen-erative properties among the different animal phyla (Sánchez Alvarado, 2000). Thus, looming large on the horizon is the following question: Why can some animals regenerate missing body parts and others can-not? To date, no satisfactory answer to this question exists. We are at odds in explaining regeneration as an evolutionary variable (Brockes et al., 2001) and, moreover, lack sufficient molecular evidence to either support or debunk the notion that regenera-tion may be a primordial metazoan attribute lost to some species for reasons that are unknown. In an effort to mechanistically address these issues, we and others have begun a systematic genetic and cellular exploration of the problem of regeneration in animals. In this essay, I aim to provide an account of these ongoing efforts and to provide an argument for the under-appreciated advantage of regenera-tion studies to inform our understanding of fundamental aspects of animal biology, including our own. A largely ignored animal model of regenera-tion that is making a comeback is the planarian, a simple platyhelminth worm (see Figure 1). Why Study Regeneration? Besides the obvious, important practical ramifications of improving human health, the study of regeneration also provides fertile and largely unexplored grounds for boosting our understanding of the basic molecular and cellular processes governing biological …