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Graduate School of Biomedical Sciences

The Rob Jackson Lab

Cell Type-Specific Expression Profiling of Clock Cells and Glia

Genome-wide studies of circadian transcription or mRNA translation have been hindered by the presence of heterogeneous cell populations in complex tissues such as nervous system. We have developed Drosophila strains that permit cell-specific and genome-wide studies of gene expression. We have used these strains, together with NextGen sequencing methods (RNA-seq) to identify hundreds of mRNAs that exhibit daily rhythms of in ribosome association (a surrogate for translation) in circadian clock cells of adult Drosophila (Huang et al, 2013). Some of these clock cells are glial astrocytes which communicate with the circadian neuronal circuitry. Thus, in related studies, we have defined the genome-wide expression profile of glial astrocytes (Huang et al, 2015; Ng et al, 2016) and identified mRNAs showing rhythmic expression in this cell type. Our studies of glia have revealed significant similarities between the gene expression profiles of fly and mammalian glial astrocytes, emphasizing the conservation of cellular and molecular mechanisms that are important for neural function. They underscore the importance of Drosophila as a genetic model for understanding the glial regulation of neuronal circuits and behavior. As circadian and sleep mechanisms are conserved between Drosophila and humans, our studies have considerable significance for understanding pathophysiological changes that affect these processes.

Brain Glial Cells and Behavior

An important goal of contemporary neuroscience research is to define the neural circuits and synaptic interactions that mediate behavior. Mechanisms regulating circadian behavior and sleep, both rhythmic behaviors, are remarkably similar in Drosophila and mammals. The molecular biology of the circadian clock, for example, is virtually identical in flies and mammals including humans (Jackson, 2011). In mammals, sleep is regulated by homeostatic and circadian processes, and the same is true of Drosophila sleep, which has characteristics in common with human sleep.In mammals, sleep is regulated by homeostatic and circadian processes, and the same is true of Drosophila sleep, which has characteristics in common with human sleep. In mammals and Drosophila, the neuronal circuits controlling circadian behavior or sleep have been the subject of intensive investigation, but roles for glial cells in the networks controlling rhythmic behavior have only begun to be defined in recent studies. Our lab was the first to document an important role for glial cells in the physiological regulation of circadian behavior (Suh and Jackson, 2007; Ng et al., 2011, 2015, 2016) . Others have shown that mammalian astrocytes regulate circadian behavior and sleep. Our more recent studies have utilized Drosophila astrocyte gene expression profiling as a basis for RNAi-based genetic screens to discover glial factors regulating circadian behavior (Ng and Jackson, 2015; Ng et al, 2016) or sleep. In similar studies, we have performed a genome-wide screen for small Drosophila non-coding RNAs (microRNAs) that regulate circadian behavior. That screen has revealed a number of microRNAs and target RNAs that are required in adult astrocytes for normal circadian behavior. Ongoing studies in the lab are focused on a number of glial factors that regulate Drosophila circadian behavior or sleep.

Jackson Fig 1

Figure 1. A novel glial protein regulating Drosophila sleep is trafficked to glial processes (green), consistent with secretion.