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CIS-regulatory integration of intrinsic transcription factors with target-derived signals in neuronal differentiation

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Title: CIS-regulatory integration of intrinsic transcription factors with target-derived signals in neuronal differentiation
Author: Tang, Chung Yiu Jonathan
Degree: Master of Science - MSc
Program: Cell and Developmental Biology
Copyright Date: 2009
Issue Date: 2010-04-27
Publisher University of British Columbia
Abstract: We now know that expression of the appropriate terminal differentiation gènes (TDG), such as neuropeptides, neurotransmitters, ion channels, etcetera, in maturing neurons is controlled by cell-specific combinations of transcription factors and by signals secreted from the neurons' target cells. However, it is unclear how thèse two regulatory inputs are integrated inside neurons. In Drosophila, target-derived Bone Morphogenetic Protein (BMP) signals and a well-characterized combinatorial code of transcription factors activate expression of the FMRFa gene in the Tv neurons. Here, I performed a cis-regulatory analysis of FMRFa in order to understand how the two factors functionally intersect. Mutant analysis reveals that 4 of the 7 known FMRFa regulators, Apterous, BMP signalling, Dachshund and Zfhl, ail regulate the expression of the Tv enhancer, a 446 bp cw-regulatory element that faithfully reproduces FMRFa expression in the Tv neurons. Within the Tv enhancer, I identified a functional module, termed HD/BRE-A, that is predicted to respond to both BMP signalling and the homeodomain transcription factor Apterous. I also verified that Apterous and the BMP factors, Mad and Medea, can directly bind to HD/BRE-A in vitro. Furthermore, transgenic analyse indicate that the positioning between the Apterous and Medea binding site is critical for Tv enhancer activation, suggesting a strict physical requirement for simultaneous association of these factors. Taken together, my results supports a model of cis-regulatory integration of BMP signaling and homeodomain transcription factors in the regulation of TDGs.
Affiliation: Science, Faculty of
URI: http://hdl.handle.net/2429/24210
Scholarly Level: Graduate

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