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Vestigial-like Family Co-Factors in Drosophila Development
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- Author / Creator
- Pimmett, Virginia L
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Cells require the ability to modulate function in response to their surroundings so that they are able to contribute to the survival of the organism. A key mechanism that allows tunable responses to changes in environment is by differential control of gene expression by transcriptional regulators. In Drosophila, the Vestigial-like (VGLL) family of transcriptional co-factors is comprised of two genes, vestigial (vg) and Tondu domain-containing Growth Inhibitor (Tgi). Regulation of these co-factors is key during development of metazoans, and their dysregulation in humans is associated with several types of cancers.
Vg, the Drosophila orthologue of the mammalian VGLL1-3 proteins, is regulated by phosphorylation at the Serine-215 residue. This phosphorylation is mediated by association with the transcription factor Scalloped (Sd), and the residue is a target of the p38 mitogen-associated protein kinase (MAPK) pathway. Interfering with phosphorylation at Serine-215 causes developmental defects in the adult Drosophila wing, as well as altering terminal specification of the embryonic somatic musculature.
Tgi, the Drosophila orthologue of the mammalian VGLL4 protein, is a recently identified second member of the VGLL gene family in Drosophila. Tgi is able to interact with Sd similarly to Vg, but Tgi and Vg are unable to form a co-complex. A potential explanation for this is that Tgi and Vg are competing and excluding the other from interaction with Sd. Ectopic expression of Tgi causes wing size reduction and fate defects in the adult wing, and this wing size reduction is dose-sensitive to the level of vg expression. Additionally, overexpression of Tgi in Drosophila Kc167 cells causes an exclusion of Vg to the cytoplasmic domain, and Tgi and Vg direct Sd to differentially regulate target genes. Finally, Tgi induces the expression of vg, setting up a negative feedback loop to repress its own activity.
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- Graduation date
- Fall 2018
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- Type of Item
- Thesis
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- Degree
- Doctor of Philosophy
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- License
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