Abstract
Glial cells constitute a large proportion of the central nervous system (CNS) and are critical for the correct development and function of the adult CNS. Recent studies have shown that specific subtypes of glia are generated through the proliferation of differentiated glial cells in both the developing invertebrate and vertebrate nervous systems. However, the factors that regulate glial proliferation in specific glial subtypes are poorly understood. To address this we have performed global gene expression analysis of Drosophila post-embryonic CNS tissue enriched in glial cells, through glial specific overexpression of either the FGF or insulin receptor. Analysis of the differentially regulated genes in these tissues shows that the expression of known glial genes is significantly increased in both cases. Conversely, the expression of neuronal genes is significantly decreased. FGF and insulin signalling drive the expression of overlapping sets of genes in glial cells that then activate proliferation. We then used these data to identify novel transcription factors that are expressed in glia in the brain. We show that two of the transcription factors identified in the glial enriched gene expression profiles, foxO and tramtrack69, have novel roles in regulating the proliferation of cortex and perineurial glia. These studies provide new insight into the genes and molecular pathways that regulate the proliferation of specific glial subtypes in the Drosophila post-embryonic brain.
Highlights
Glial cells constitute a large proportion of the central nervous system (CNS) and are critical for the correct development and function of the adult CNS
Two major questions arise from these studies of glial proliferation: (1) What are the factors that define glial subtype identity? (2) What are the factors and pathways that regulate the proliferation of specific glial subtypes? We have recently shown that proliferation of cortex and perineurial glia in the post-embryonic brain is driven by the fibroblast growth factor (FGF) and insulin receptor (InR)/mechanistic target of rapamycin pathways, which differentially regulate cortex and perineurial glial proliferation (Avet-Rochex et al, 2012)
We have recently shown that the proliferation of two glial subtypes in the Drosophila post-embryonic brain is regulated through the concerted action of the FGF and InR/mechanistic target of rapamycin (mTOR) pathways
Summary
Glial cells constitute a large proportion of the central nervous system (CNS) and are critical for the correct development and function of the adult CNS. We show that two of the transcription factors identified in the glial enriched gene expression profiles, foxO and tramtrack, have novel roles in regulating the proliferation of cortex and perineurial glia These studies provide new insight into the genes and molecular pathways that regulate the proliferation of specific glial subtypes in the Drosophila postembryonic brain. In the mammalian central nervous system (CNS) glia have been shown to regulate synaptic transmission through modulation of neurotransmitter levels at ‘tripartite synapses’ (Perea et al, 2009) These functions are performed by different classes of glia, such as astrocytes that associate with neuronal cell bodies and synapses, and oligodendrocytes that form myelin sheaths around axons (Freeman and Doherty, 2006). The genes that regulate the cell division of astrocytes are not known and the genetic regulation of proliferation of specific glial subtypes in Drosophila has only begun to be explored
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