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Description
Proper cell growth and differentiation requires the integration of multiple signaling pathways that are maintained by various post-translational modifications. Many proteins in signal transduction pathways are conserved between humans and model organisms. My dissertation characterizes four previously unknown manners of regulation in the Drosophila Decapentaplegic (Dpp) pathway, a pathway within TGF-beta family. First, I present data that the Dpp signal transducer, Mothers Against Dpp (Mad), is phosphorylated by Zeste-white 3 (Zw3), a kinase involved in the Wingless pathway. This phosphorylation event occurs independently of canonical phosphorylation of Mad by the Dpp receptor. Using ectopic expression of different alleles of Mad, I show that Zw3 phosphorylation of Mad occurs during the cell cycle in pro-neuronal cells and the loss of phosphorylation of Mad by Zw3 results in ectopic neuronal cells. Thus, Mad phosphorylation by Zw3 is necessary for cell cycle control in pro-neuronal cells. Second, I have shown that the regulator dSno, which has previously been shown to be a TGF-beta antagonist and agonist, is also a Wingless pathway antagonist. Loss of function flip-out clones and ectopic expression of dSno both resulted in changes of Wingless signaling. Further analysis revealed that dSno acts at or below the level of Armadillo (Arm) to inhibit target gene expression. Third, I have demonstrated that the protein Bonus, which is known to be involved in chromatin modification, is required in dorsal-ventral patterning. Further experiments discovered that the chromatin modifier is not only a necessary Dpp agonist, but it is also necessary for nuclear localization of Dorsal during Toll signaling. Last, I showed that longitudinal lacking-like (lola-like) is also required in dorsal-ventral patterning. The loss of maternally expressed lola-like prevents dpp transcription. This shows that lola-like is integral in the Dpp pathway. The study of these four proteins integrates different signaling pathways, demonstrating that the process of development is a web of connections rather than a linear pathway.
ContributorsQuijano, Janine C (Author) / Newfeld, Stuart J (Thesis advisor) / Goldstein, Elliott (Committee member) / Chandler, Douglas (Committee member) / Capco, David (Committee member) / Arizona State University (Publisher)
Created2014
Description
Transgenic experiments in Drosophila have proven to be a useful tool aiding in the
determination of mammalian protein function. A CNS specific protein, dCORL is a
member of the Sno/Ski family. Sno acts as a switch between Dpp/dActivin signaling.
dCORL is involved in Dpp and dActivin signaling, but the two homologous mCORL
protein functions are unknown. Conducting transgenic experiments in the adult wings,
and third instar larval brains using mCORL1, mCORL2 and dCORL are used to provide
insight into the function of these proteins. These experiments show mCORL1 has a
different function from mCORL2 and dCORL when expressed in Drosophila. mCORL2
and dCORL have functional similarities that are likely conserved. Six amino acid
substitutions between mCORL1 and mCORL2/dCORL may be the reason for the
functional difference. The evolutionary implications of this research suggest the
conservation of a switch between Dpp/dActivin signaling that predates the divergence of
arthropods and vertebrates.
determination of mammalian protein function. A CNS specific protein, dCORL is a
member of the Sno/Ski family. Sno acts as a switch between Dpp/dActivin signaling.
dCORL is involved in Dpp and dActivin signaling, but the two homologous mCORL
protein functions are unknown. Conducting transgenic experiments in the adult wings,
and third instar larval brains using mCORL1, mCORL2 and dCORL are used to provide
insight into the function of these proteins. These experiments show mCORL1 has a
different function from mCORL2 and dCORL when expressed in Drosophila. mCORL2
and dCORL have functional similarities that are likely conserved. Six amino acid
substitutions between mCORL1 and mCORL2/dCORL may be the reason for the
functional difference. The evolutionary implications of this research suggest the
conservation of a switch between Dpp/dActivin signaling that predates the divergence of
arthropods and vertebrates.
ContributorsStinchfield, Michael J (Author) / Newfeld, Stuart J (Thesis advisor) / Capco, David (Committee member) / Laubichler, Manfred (Committee member) / Arizona State University (Publisher)
Created2019