Modulation of pha-4/FoxA and C. elegans Foregut Development by the Novel Gene smg-8
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CitationRosains, Jacqueline. 2012. Modulation of pha-4/FoxA and C. elegans Foregut Development by the Novel Gene smg-8. Doctoral dissertation, Harvard University.
AbstractFoxA transcription factors are central regulators of gut development in all species. In C. elegans, pha-4/FoxA is necessary to generate cells of the foregut, or pharynx. FoxA factors need to be precisely regulated for proper development, yet we know very little about FoxA regulation. To look for potential genes that act as pha-4 regulators, the Mango lab previously conducted two screens for suppressors of the lethality associated with a partial loss of pha-4 activity. Both screens uncovered smg-8, a novel gene that is highly conserved amongst metazoans. Interestingly, the human homolog of smg-8 is amplified in some breast cancers, which also depend on FoxA1. This observation makes smg-8 a very exciting gene to investigate. The goal of my thesis is to analyze smg-8 to better understand its function and potential role as a candidate regulator of pha-4/FoxA, using C. elegans as a model system. In this thesis, I show that C. elegans smg-8 does not have a role in the Nonsense Mediated Decay pathway. I find that smg-8 modulates pha-4 protein levels during embryonic development. This work is the first direct evidence that smg-8 is a modulator of pha-4. I used biochemical and bioinformatic approaches to uncover possible partners of smg-8. These approaches identified several interesting candidates that will help place C. elegans smg-8 in a functional pathway. This work has expanded our understanding of smg-8 function and lays the foundation for further investigation of the role of this novel gene as a regulator of pha-4/FoxA in C. elegans.
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