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Title: | MOLECULAR MECHANISMS OF SPINAL MUSCULAR ATROPHY IN THE ZEBRAFISH MODEL | Authors: | SEE ZHENWEI KELVIN | Keywords: | Spinal muscular atrophy, neurodegeneration, alternative splicing, in vivo calcium imaging, Schwann cells | Issue Date: | 14-Aug-2012 | Citation: | SEE ZHENWEI KELVIN (2012-08-14). MOLECULAR MECHANISMS OF SPINAL MUSCULAR ATROPHY IN THE ZEBRAFISH MODEL. ScholarBank@NUS Repository. | Abstract: | Spinal Muscular Atrophy (SMA) is a progressive neurodegenerative disease specifically affecting lower motor neurons (MN) in the spinal cord. Homozygous loss of ubiquitously expressed Survival of Motor Neuron (SMN1) is causative of SMA but molecular mechanisms leading to the motor neuron specific phenotypes remain unclear. Using transcriptome analyses, I identified a novel candidate, neurexin, that is strongly down-regulated and displays changes in alternative splicing patterns in a zebrafish model for SMA. To monitor activity of MNs and Schwann cells in vivo, I generated two novel Ca2+ sensor transgenic lines and provide evidence that there are significant changes in the excitability of both cell types at the neuromuscular junction in this SMA model. Taken together, I propose that SMN deficiency causes altered splicing of neurexin, which affects motor axon excitability, and that Schwann cells display primary defects in excitability possibly contributing to the pathology of SMA in a non-cell autonomous manner. | URI: | http://scholarbank.nus.edu.sg/handle/10635/35664 |
Appears in Collections: | Ph.D Theses (Open) |
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01SeeZWK.pdf | 9.76 MB | Adobe PDF | OPEN | None | View/Download | |
02SeeZWK.pdf | 9.66 MB | Adobe PDF | OPEN | None | View/Download | |
03SeeZWK.pdf | 9.92 MB | Adobe PDF | OPEN | None | View/Download | |
04SeeZWK.pdf | 2.24 MB | Adobe PDF | OPEN | None | View/Download |
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