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Maintenance of transcription factor networks in mature neurons

University of British Columbia

The lifelong identity and function of a neuron is dictated by the set of effector genes it expresses in its terminally differentiated state. Neuron-specific effector gene expression is established and maintained by networks of transcription factors. How elaborate cascades of transcription factors establish neuronal identities during development has been studied extensively; however, how transcription factor networks are maintained in mature neurons to maintain effector gene expression remains poorly understood. I used the well-characterized transcription factor networks in Drosophila Tv1 and Tv4 neurons to further understand how transcription factor networks are maintained in mature neurons. I focused on the transcription factors Apterous and Dimmed, and investigated the cis- and trans- regulatory transcriptional mechanisms that govern initiation and maintenance of their expression. I previously identified a 756 bp genomic region (dimm.K1) upstream of dimmed that is sufficient to initiate and maintain reporter expression in Tv1 and Tv4 neurons. Here I characterized the trans-regulatory inputs of dimm.K1 reporter expression. I found that different transcriptional inputs are required for initiation vs. maintenance of dimm.K1 reporter expression. Further, inputs required for maintenance differ not only between cell subtypes (Tv1 vs. Tv4) but also between individual cells of the same subtype (Tv1 neurons in thoracic segments 1 and 3). I also compared apterous initiation and maintenance. My previous work had identified a 3.845 kb genomic region (ap.K1) upstream of apterous that is sufficient to initiate, but not maintain, reporter expression in Tv1 and Tv4 neurons. In this thesis I show that the addition of a region with putative TRE activity to the ap.K1 initiation element is sufficient to add maintenance of reporter expression in Tv1 and Tv4 neurons. Overall, I show that a variety of mechanisms can maintain the expression of transcription factors in mature neurons, and that these are different and more varied than the mechanisms of initiation. Furthermore, for any single transcription factor, the initiation mechanisms that are shared by different cell subtypes can diverge into diverse cell-specific maintenance mechanisms.

Text

2018-01-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/60132

Cell and Developmental Biology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/