Multiple lineages enable robust development of the neuropil-glia architecture in adult Drosophila

Abstract

Neural remodeling is essential for the development of a functional nervous system and has been extensively studied in the metamorphosis of Drosophila. Despite the crucial roles of glial cells in brain functions, including learning and behavior, little is known of how adult glial cells develop in the context of neural remodeling. Here, we show that the architecture of neuropil-glia in the adult Drosophila brain, which is composed of astrocyte-like glia (ALG) and ensheathing glia (EG), robustly develops from two different populations in the larva: the larval EG and glial cell missing-positive (gcm +) cells. Whereas gcm + cells proliferate and generate adult ALG and EG, larval EG dedifferentiate, proliferate and redifferentiate into the same glial subtypes. Each glial lineage occupies a certain brain area complementary to the other, and together they form the adult neuropil-glia architecture. Both lineages require the FGF receptor Heartless to proliferate, and the homeoprotein Prospero to differentiate into ALG. Lineage-specific inhibition of gliogenesis revealed that each lineage compensates for deficiency in the proliferation of the other. Together, the lineages ensure the robust development of adult neuropil-glia, thereby ensuring a functional brain.

Drosophila ßHeavy-Spectrin is required in polarized ensheathing glia that form a diffusion-barrier around the neuropil

“…About 112 ensheathing glial cells expressing 83E12-Gal4 can be detected in the third instar larva with only few ensheathing glial cells in the brain lobes (n = 5, with 110, 112, 112, 114, and 116 83E12-Gal4 positive cells, median = 112) (Fig. 3a, m), which corresponds to previously determined numbers 27,35,40,46,47 and matches the annotations made in the TEM volume mentioned above. During the subsequent pupal development, the number of the 83E12-Gal4 positive ensheathing glial cell population increases more than 1,100 ensheathing glial cells in the adult (ventral nerve cord and brain without optic lobes, number determined using Imaris) (Fig.…”

“…It is unclear whether all larval ensheathing glia degenerate or whether some survive to participate in the formation of adult ensheathing glia 35,46 . To test whether ensheathing glial cells are competent to divide, we expressed activated FGF-receptor which is known to trigger perineurial glial proliferation 48,49 .…”

Drosophila ßHeavy-Spectrin is required in polarized ensheathing glia that form a diffusion-barrier around the neuropil

“…Some of the larval ensheathing glia are diploid and block of cell proliferation reduces their number by 38 %, suggesting that proliferation of these cells contributes to the increase of ensheathing glial complexity. These finding support the notion that some larval ensheathing glia can dedifferentiate, proliferate and redifferentiate to form the more complex adult ensheathing glia (Kato et al, 2020).…”

“…About 112 ensheathing glial cells expressing 83E12-Gal4 can be detected in the third instar larva with only few ensheathing glial cells in the brain lobes (n=5, with 110, 112, 112, 114, and 116 83E12-Gal4 positive cells, median = 112) (Figure 3A, M), which corresponds to previously determined numbers (Beckervordersandforth et al, 2008;Kato et al, 2020;Omoto et al, 2015;Peco et al, 2016;Pereanu et al, 2005) and matches the annotations made in the TEM volume mentioned above. During the subsequent pupal development, the number of the 83E12-Gal4 positive ensheathing glial cell population increases more than 1,100 ensheathing glial cells in the adult (ventral nerve cord and brain without optic lobes, number determined using Imaris) (Figure 3C,N).…”

“…It is unclear whether all larval ensheathing glia degenerate or whether some survive to participate in the formation of adult ensheathing glia (Kato et al, 2020;Omoto et al, 2015).…”