Planarians are free-living flat worms that are best known for their regenerative capacity. For example, after surgical bisection of the animal in either the vertical or horizontal plane each half of the animal will regenerate the missing structures. In fact, a fragment as small as 1/279th the size of the original individual has the capacity to regenerate into an entire animal. The key to the amazing regenerative prowess of these creatures is a population of cells known as neoblasts that are distributed throughout the body of the animal. Neoblasts are totipotent cells that are the only dividing cells in the animal. The division progeny of neoblasts replace cells lost during normal cellular turnover in the animal. After injury, however, neoblasts migrate to the wound site, divide, and their progeny eventually replace the missing structures. Thus, neoblasts are the planarian equivalent of stem cells making these unique organisms an excellent model system for studying stem cell biology. We have recently identified over 70 microRNAs - small RNA molecules that regulate gene expression post-transcriptionally - from the planarian Schmidtea mediterranea. We are currently working to determine the expression patterns of each miRNA, identify mRNA targets that are regulated by each miRNA, and to identify the biological functions of each miRNA. It is likely that understanding how regeneration in planarians is regulated will provide insight into the biology of stem cells in other organisms, including humans.

More recently we have identified a second class of diverse ~32 nt small RNAs that strongly resemble vertebrate and insect piRNAs and map to hundreds of thousands of loci in the S. mediterranea genome.  piRNAs that have been identified in Drosophila and vertebrates are small RNAs that associate with members of the PIWI protein  and are expressed in germ cells.  One function of piRNAs is to preserve the integrity of the germline genome by silencing transposons, though they also participate in epigenetic and post-transcriptional gene regulation.  Previously, Reddien and Sanchez-Alvarado reported that the PIWI proteins SMEDWI-1 and SMEDWI-2 are expressed in neoblasts and that SMEDWI-2 is required for regeneration and homeostasis.  We have found that the planarian piRNAs are  predominantly expressed in neoblasts and are not restricted to the germline. RNAi knockdown of either SMEDWI-2 or a newly identified PIWI protein, SMEDWI-3, impairs regeneration and homeostasis and decreases the levels of both piRNAs and neoblasts.  Therefore, SMEDWI-2 and SMEDWI-3 and required for piRNA expression, regeneration, and neoblast function in S. mediterranea.  We are currently working to further elucidate the function of this remarkably diverse class of RNAs in neoblast function and regeneration.