CAREER: Molecular Mechanisms Regulating Neural Regeneration in Planarians

Western Michigan University, Kalamazoo MI

Investigators

Abstract

It is not understood why some organisms (such as planarian flatworms) are easily able to regenerate their brain and nervous system, while others (such as humans) cannot. Planarian flatworms can impressively regenerate a new head and brain, yet the signals that control their adult stem cells, causing them to divide and produce these new tissues, are not known. This project seeks to understand the molecular identity and function of these signals - particularly, how new tissues determine when their regeneration is complete, and how the individual identity of the regenerated cells that rebuild neural circuits is established. These goals will be pursued in flatworms using a combination of sophisticated genetic, molecular, cell-biological, microscopy and imaging techniques. The results of these studies will provide increased knowledge about how new tissues and organs are patterned after stem cell growth, and could open novel research avenues into potential ways to induce neural regeneration. Undergraduate students will contribute substantially to this research, and this project includes an extensive set of outreach goals to promote diversity and interest in post-secondary STEM education by connecting with local middle and high students, their parents and STEM instructors, and increasing their classroom research experiences. This project is an integrated research, education, and outreach initiative focused on the role of planar cell polarity (PCP) as a tissue-level organizing mechanism that links adult stem cell biology to reparative neurogenesis and morphology. The objectives of this project are: 1) To characterize interactions between PCP signaling and neural stem cell proliferation/differentiation, by investigating the effects of PCP loss on neural stem cells and their progeny; 2) To test the hypothesis that multiple neuronal subtypes require PCP to establish proper regenerative patterning, using marker analyses and RNA interference enhancer/suppressor screens; 3) To identify PCP protein localization in neural and/or non-neural cell types; 4) To incorporate and develop a new teaching initiative in the upper-division undergraduate curriculum, involving undergraduates in research in the classroom; and 5) To expand a community outreach pilot program to other area middle and high schools where exposure to STEM practicum experiences is limited. The proposed work will elucidate the mechanisms by which PCP coordinates with neural stem cells and their progeny to regenerate nervous tissue of precisely the correct size, shape, and orientation.