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Dissertation
Distribution and Regulation of Fragile X Granules in the Spinal Cord
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2020
DOI:
https://doi.org/10.17918/00001380
Abstract
Axons are remarkably complex neuronal domains that comprise multiple morphologically and functionally diverse compartments. Whether establishing and maintaining these compartments requires that local protein synthesis is differentially regulated across axonal compartments, and how such regulation might differ among neuron types, is unclear. To address this, we examined axons in the postnatal mouse spinal cord for the presence of Fragile X Granules (FXGs), a class of exclusively axonal ribonucleoprotein particles. FXGs contain Fragile X related RNA-binding proteins FXR2P, FXR1P, and FMRP and associate with ribosomes and mRNA. In brain circuits, FXGs are present in specific axonal subsets and exhibit circuit-dependent RNA-binding protein and mRNA composition. However, whether FXGs are also found in spinal cord axons is unknown. Here, I used a combination of genetic, immunofluorescence, and quantitative colocalization approaches to show that specific subsets of axons in the rodent spinal cord contain FXGs. FXGs are found along the length of the spinal cord but are most abundant in cervical forelimb circuits. As in brain, spinal cord FXGs contain FMRP and associate with rRNA. In cervical circuits, FXGs are present in particular axonal subsets including A-fibers, IB4+ nonpeptidergic C-fibers, [alpha]-motor axons, ascending nociceptive fibers, and propriospinal interneuron axons. In axons that traverse the CNS and PNS, FXGs are enriched within CNS compartments. Analyses of large diameter axons revealed that FXGs localize close to the plasma membrane. Evaluation of Fmr1 null mice showed that, in dorsal root, FMRP regulates FXG abundance in IB4+ C-fibers, but not other examined axon populations. Together, these findings suggest that FXGs regulate local translation in specific axons in spinal circuits in response to signaling at the plasma membrane.
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Details
- Title
- Distribution and Regulation of Fragile X Granules in the Spinal Cord
- Creators
- Molly Elizabeth Mitchell
- Contributors
- Michael R. Akins (Advisor)Daniel Marenda (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- 158, [29] pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 991014695136804721