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The Role of Notch Signaling in Neurotransmitter Phenotype Specification in Xenopus Laevis
Harper, Michael S.
Harper, Michael S.
Abstract
The development of a functional nervous system depends on individual neurons acquiring an appropriate neurotransmitter phenotype. In the developing spinal cord, neurons often display different fates in a "salt and pepper" pattern, and the mechanism by which this non-random dispersed patterning occurs remains largely unknown. However, given the role of Notch signaling in neurogenesis, the Notch pathway is a possible mediator because of its role in lateral inhibition. We hypothesized that Notch signaling is involved in the decision between GABAergic and glutamatergic fates and that activating Notch signaling in vivo would result in more neurons acquiring a glutamatergic neurotransmitter phenotype, while inactivating Notch signaling would increase GABAergic phenotypes. To test this hypothesis, we activated Notch signaling by injecting mRNA for X-Notch ICD and inactivated Notch signaling by injecting mRNA for xSu(H) DNA Binding Mutant, an inactive form of the transcription factor xSu(H). Embryos injected with X-Notch ICD lacked expression of the glutamate transporter xVGlut1 and the GABA transporter xGAT1, and embryos injected with xSu(H) DBM showed widespread ectopic expression of neuronal marker xNBT and xVGlut1. Embryos did not show ectopic expression of xSlug, suggesting that ectopic cells were not derived from the neural crest. HNK-1 immunohistochemistry showed ectopic expression in what appeared to be aberrant neural processes, indicating that the ectopic cells may be differentiated neurons or glia. We are now attempting to activate inducible xSu(H) DBM-GR and X-Notch ICD-GR at different developmental stages to determine the later effects of Notch activation, and if ectopic expression only occurs during a certain window of competency.
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Thesis is part of Honors ETD pilot project, 2008-2013. Migrated from Dspace in 2016.
Date
2009-05-14
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Keywords
Neurobiology, Developmental biology
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Neuroscience