Flatworms (planaria) have a remarkable ability to regenerate their bodily structures; for example, when a worm is cut in two, the tail half will grow a new head, and similarly the half with the head will regenerate a new tail. The drug praziquantel (or PZQ) has a surprising effect on the regenerating worm; it results in a two-headed animal. The goal of this project is to understand how, in this organism, stem cells can be re-programmed to regenerate a head rather than a tail. This project will generate for the community both scientific resources (for example databases of DNA and protein sequences) and educational resources, including kits that can be used by both schools and universities as aids to teaching stem cell biology. The researchers will organize courses for high school teachers, and provide interdisciplinary research opportunities in stem cell biology and bioinformatics for both graduate students and undergraduates.
The hypothesis to be tested in this project is that in the regenerating planarian Dugesia japonica the drug praziquantel (PZQ) activates a neuronal Ca2+ channel (Cav1A) to alter neurotransmitter levels within the excitable cell niche and thereby miscue stem cell differentiation. Two opposing neurotransmitter pathways are proposed that control head versus tail polarity by differentially impacting muscle biology where known planarian polarity cues (e.g. Wnts) reside. This hypothesis will be tested using both unbiased (systems-level) and targeted (candidate gene) approaches to gain insight into the target of action of PZQ and the pathways that control stem cell differentiation in the anterior-posterior axis.