Studying planarian regeneration: insights into how polarity is re-established

Neurodegenerative and cardiovascular diseases, as well as stroke, infection and injury, require therapies that aim to replace lost, damaged or inoperative tissues. Regenerative medicine is therefore a major focus of medical research. Whereas regeneration in humans is limited, several vertebrates, such as salamanders and fish, can regenerate amputated body parts with high efficiency (reviewed in Stoick-Cooper et al., 2007). The master of regeneration is, however, the planarian flatworm. Planarians are free-living Platyhelminthes that can regenerate any part of the body, including the central nervous system (CNS). In addition to Dugesia japonica and Girardia tigrina, Schmidtea mediterranea is one of the most commonly used species in planarian research. This freshwater planarian is small in size (0.1-2 cm), has a diploid genome of about 800 Mb distributed on four chromosomes, which accounts for about 30,000 predicted genes (Cantarel et al., 2008), and can reproduce sexually as well as asexually by fission. The regenerative abilities of planarians depend on a large population of somatic stem cells (reviewed in HandbergThorsager et al., 2008). This feature, which, among bilaterians, is unique to planarian flatworms, means that planarians can serve as an in vivo Petri dish for the study and manipulation of stem cells in their natural environment. In recent years, the unique properties of planarians, combined with the development of new technologies and the genome sequencing of S. mediterranea (http://genome.wustl.edu/genomes), have sparked planarian research. The application of RNA interference (RNAi) for gene-specific knockdown in planarians (Sanchez Alvarado and Newmark, 1999; Newmark et al., 2003) allowed identification of several genes and signal transduction pathways that regulate different aspects of regeneration, such as polarity and patterning, and stem cell proliferation, maintenance and differentiation (Guo et al., 2006; Oviedo et al., 2008; Adell et al., 2009; Rink et al., 2009; Felix and Aboobaker, 2010; Fernandez-Taboada et al., 2010; Scimone et al., 2010). The amenability to efficient RNAi treatments, rapid development of clear phenotypes and established cell biological readouts, combined with new post-genomic technologies, make planarians an outstanding tool for gene discovery and can reveal unidentified functions of known and unknown genes involved in human regeneration, development and disease. Table 1 summarises several planarian genomic regions that have significant similarity to human disease-related genes. In this Primer article, we review the stateof-the-art of planarian research, focusing on stem cells, neural regeneration and reestablishment of polarity, and discuss how the knowledge gained from planarian research might be translated to higher organisms. We aim to bring the attention of the broader scientific community to these amazingly plastic animals as a promising model organism for the rapidly progressing fields of regenerative medicine and bioengineering.