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Title: The role of mRNA splicing factor B52 in regulating choline acetyltransferase and larval locomotion in Drosophila
Author: Liu, Boyin
ISNI:       0000 0004 5349 8092
Awarding Body: Prifysgol Bangor University
Current Institution: Bangor University
Date of Award: 2014
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This work investigates how two daughter cells, which arise from the same progenitor cell, can mature in two distinct neurons. Single cell transcriptome analysis of the two sibling cells vMP2 and dMP2 in the Drosophila central nervous system revealed that the expression level of the mRNA splicing factor B52 is around 45 times higher in dMP2 than that in vMP2 in stage 17 embryos. Given that the axons of vMP2 and dMP2 project in opposite directions, the up-regulation of B52 in the dMP2 cell suggests that B52 might play a role in the selection of synaptic partners before synaptogenesis takes place. This process involves the selection of neurotransmitter expression, which subsequently contributes to control of locomotion in late stage embryos and larvae. Using mutants created in this study, which are devoid of B52 RNA in larval stages, I first discovered that the expression level of choline acetyltransferase (ChAT) is elevated as a result of reduced B52 activity. This increase in ChAT correlates with the presence of an aberrantly spliced ChAT mRNA in embryos and mutant larvae with reduced B52 levels. In addition to this, abnormal behaviours were observed in hatching embryos with reduced B52 levels as well as in 36hrs post hatching larvae devoid of B52 mRNA. Given the upregulation of ChAT, the resulting high levels of acetylcholine may interfere with hatching by triggering paralysis of the larval muscle through its highly sensitive and abundant receptors thereby rendering the larvae unable to move. Interestingly, the behaviour and physical appearance of 36hrs post hatching larvae devoid of B52 RNA highly resemble that seen in mutants defective in the ecdysone receptor (EcR), especially the lack of motion and reduced larval body size. This nuclear hormone receptor is closely linked with growth and development. More importantly, genomic studies have identified EcR as a potential splicing target of B52. These results suggest that the synthesis of acetylcholine by ChAT is critical for the differentiation of the dMP2 sibling cells and normal movement of larvae in a B52-dependent manner.
Supervisor: Bossing, Torsten Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available