Origin and development of neuropil glia of the Drosophila larval and adult brain: Two distinct glial populations derived from separate progenitors

Abstract

Glia comprise a conspicuous population of non-neuronal cells in vertebrate and invertebrate nervous systems. Drosophila serves as a favorable model to elucidate basic principles of glial biology in vivo. The Drosophila neuropil glia (NPG), subdivided into astrocyte-like (ALG) and ensheathing glia (EG), extend reticular processes which associate with synapses and sheath-like processes which surround neuropil compartments, respectively. In this paper we characterize the development of NPG throughout fly brain development. We find that differentiated neuropil glia of the larval brain originate as a cluster of precursors derived from embryonic progenitors located in the basal brain. These precursors undergo a characteristic migration to spread over the neuropil surface while specifying/differentiating into primary ALG and EG. Embryonically-derived primary NPG are large cells which are few in number, and occupy relatively stereotyped positions around the larval neuropil surface. During metamorphosis, primary NPG undergo cell death. Neuropil glia of the adult (secondary NPG) are derived from type II lineages during the postembryonic phase of neurogliogenesis. These secondary NPG are much smaller in size but greater in number than primary NPG. Lineage tracing reveals that both NPG subtypes derive from intermediate neural progenitors of multipotent type II lineages. Taken together, this study reveals previously uncharacterized dynamics of NPG development and provides a framework for future studies utilizing Drosophila glia as a model.

Monitoring cell-cell contacts in vivo in transgenic animals

“…We have also observed that the astrocytes surrounding the ventral sectors of the antennal lobe also extend branches into the subesophageal zone. This suggests that this particular astrocyte might bridge the function between the antennal lobe and the subesophageal zone, consistent with previous publications that imply a close functional relationship between these two brain areas in the larval brain (Omoto et al, 2015). Finally, we have observed that the size of the cell bodies of astrocytes that branch in the mushroom body are larger than those that branch in the antennal lobe.…”

“…Interestingly, some of those GFP + astrocytes infiltrate not only the antennal lobes, but also the dorsal part of the subesophageal zone (Fig. 6C, arrowhead in middle panel), consistent with previous findings of astrocytes in larval central brain (Omoto et al, 2015). Moreover, we found that the cell body size of the GFP + astrocytes surrounding the mushroom bodies (induced by the MB247 driver) is larger than that of the astrocytes close to the antennal lobes (induced by the Orco driver).…”

“…Third, we have observed that some of the astrocytes extend branches into two different functional areas of the brain (the antennal lobe and the subesophageal zone). This suggests that these particular astrocytes might bridge the function between these two brain areas, which is consistent with previous publications that imply a close functional relationship between these brain areas (Omoto et al, 2015). Based on these results, we anticipate that this synthetic genetic system will be useful for investigating cell-cell interactions during development in vivo, and has the potential to unveil wiring diagrams of neurons in brain circuits (Meinertzhagen and Lee, 2012;Lichtman and Denk, 2011).…”

Drosophila astrocytes cover specific territories of CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch

“…Like their mammalian counterparts, Drosophila astrocytes extend processes that infiltrate the synaptic neuropil, and tile with one another to occupy non-overlapping territories (Awasaki et al, 2008;Doherty et al, 2009;Omoto et al, 2015;Stork et al, 2014). Drosophila astrocytes respond to neuronal activity with altered transporter expression and intracellular calcium dynamics (Muthukumar et al, 2014;Stork et al, 2014), they influence CNS synapse number during neural circuit formation (Muthukumar et al, 2014) and modulate locomotor behavior, seizures and olfactory processing (Liu et al, 2014;Rival et al, 2004;Stacey et al, 2010;Stork et al, 2014).…”

Hexapoda: A Drosophila’s View of Development

“…Most, if not all neuropil glia (both ensheathing and astrocytelike), are generated from a small number of type II lineages in the posterior brain. Interestingly, the identity of these secondary neuro-glioblasts is different from that of the embryonic neuroblasts that had produced primary glia (Omoto et al 2015 ). Another rich source for secondary glia is the optic lobe (Edwards et al 2012 ).…”