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Name(s): Edgar Wang, Wayne Shu and Justin Yuan High School(s): Troy High School, Troy, MI

Name(s): Edgar Wang, Wayne Shu and Justin Yuan High School(s): Troy High School, Troy, MI Mentor: Dr. Michael Chopp Project Title: MicroRNA 17-92 Cluster Mediates Sonic Hedgehog Induced Neurogenesis on Neural Stem Cells After Stroke.

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Name(s): Edgar Wang, Wayne Shu and Justin Yuan High School(s): Troy High School, Troy, MI

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  1. Name(s): Edgar Wang, Wayne Shu and Justin Yuan High School(s): Troy High School, Troy, MI Mentor: Dr. Michael Chopp Project Title: MicroRNA 17-92 Cluster Mediates Sonic Hedgehog Induced Neurogenesis on Neural Stem Cells After Stroke Background and Purpose: Ischemic stroke induces neurogenesis in the subventricular zone (SVZ). MicroRNAs (miRNAs) are small non-coding RNA molecules that provide a novel mechanism for gene regulation. Few miRNAs have had roles described in neurogenesis. We investigated the role of miR-17-92 cluster, and its interaction with Sonic hedgehog (Shh) signaling, in neural stem cells (NSCs) after stroke. Methods: Using real-time RT-PCR with laser capture microdissection, components of miR-17-92 cluster were investigated in the SVZ of rats subjected to middle cerebral artery occlusion. To examine the effect of Shh, NSCs were treated with recombinant mouse Shh (rmShh) in the presence of cyclopamine, a Shh-receptor blocker. The miR-17-92 cluster was delivered into NSCs via electroporation to test its effects on neurogenesis. Results: Stroke increased expression of miR-17-92 cluster in harvested SVZ NSCs. Overexpression of the miR-17-92 cluster increased proliferation and reduced expression of phosphatase and tensin homolog (PTEN), a cell proliferation suppressor. rmShh increased miR-17-92 cluster expression. Addition of cyclopamine suppressed rmShh-induced expression of miR-17-92 cluster. Conclusion: The miR-17-92 cluster exhibits significant neuroregenerative effects in SVZ NSCs after stroke and mediates the Shh-induced neurogenesis. These novel data suggest that miR-17-92 may be an attractive therapeutic target for treatment of neurodegenerative diseases.

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