Transcriptional Regulation of the foraging Gene and its Associated Behaviours

The genetic underpinnings of animal behaviour are exceedingly complex. The behavioural effects of a gene often depend on environmental conditions, as the ability to adjust to new conditions is essential for fitness. Furthermore, genetic background can affect behaviour, introducing additional variability in behavioural responses. To complicate the study of behavioural genetics further, many genes that regulate behavioural phenotypes are themselves very complex genes, with several gene products and functions. One example of such a complex gene is the foraging gene in Drosophila melanogaster, which encodes a signaling protein that is involved in regulating many phenotypes, including feeding behaviour, metabolism, learning and memory, and sleep. foraging has four promoters, twenty-one transcripts, and nine distinct open reading frames (ORFs). The putative FOR isoforms encoded by these ORFs share the same 3’ protein kinase domain and cGMP binding domains but differ in their subcellular localization and self-regulatory domains. This complex molecular structure allows for the production of different gene products at different times in different tissues, likely using different transcriptional regulators. This thesis examines different mechanisms of transcriptional regulation of the foraging gene and the role of those mechanisms in Drosophila behaviour. Using gene expression measurements, behavioural assays and transgenic tools I investigate the regulatory underpinnings of differences in adult Drosophila feeding behaviour, and larval food-related behaviours. The results provide a complex picture of pleotropic behavioural regulation by different products generated by a single gene. I found that strain differences in adult, but not larval, feeding behaviour are regulated by the transcriptional regulator G9a, a histone methyl transferase which differentially methylates foraging’s promoters. Select larval food-related behaviours are under regulation by Pumilio, an mRNA binding protein that binds the 3’ UTR of foraging mRNA transcripts. Furthermore, I show that foraging and its transcriptional regulators play a role in the behavioural response to nutritional stress. Collectively, my thesis provides new insights into the complex molecular mechanisms (genetic, epigenetic and post-transcriptional) that underlie the regulation of behavioural pleiotropy of foraging, a complex gene.Ph.D.2021-11-11 00:00:0