Multipotent neural stem cells generate glial cells of the central complex through transit amplifying intermediate progenitors in Drosophila brain development

Abstract

The neural stem cells that give rise to the neural lineages of the brain can generate their progeny directly or through transit amplifying intermediate neural progenitor cells (INPs). The INP-producing neural stem cells in Drosophila are called type II neuroblasts, and their neural progeny innervate the central complex, a prominent integrative brain center. Here we use genetic lineage tracing and clonal analysis to show that the INPs of these type II neuroblast lineages give rise to glial cells as well as neurons during postembryonic brain development. Our data indicate that two main types of INP lineages are generated, namely mixed neuronal/glial lineages and neuronal lineages. Genetic loss-of-function and gain-of-function experiments show that the gcm gene is necessary and sufficient for gliogenesis in these lineages. The INP-derived glial cells, like the INP-derived neuronal cells, make major contributions to the central complex. In postembryonic development, these INP-derived glial cells surround the entire developing central complex neuropile, and once the major compartments of the central complex are formed, they also delimit each of these compartments. During this process, the number of these glial cells in the central complex is increased markedly through local proliferation based on glial cell mitosis. Taken together, these findings uncover a novel and complex form of neurogliogenesis in Drosophila involving transit amplifying intermediate progenitors. Moreover, they indicate that type II neuroblasts are remarkably multipotent neural stem cells that can generate both the neuronal and the glial progeny that make major contributions to one and the same complex brain structure.

Drosophila intermediate neural progenitors produce lineage-dependent related series of diverse neurons

“…1H-W). The complex yet stereotyped clone morphologies argue that each type II NB produces a characteristic set of diverse neuronal offspring in addition to glia (Izergina et al, 2009;Viktorin et al, 2011;Yu et al, 2013;Viktorin et al, 2013).…”

“…4). Not seeing the later-derived glia should not affect our neuron birthdating (Viktorin et al, 2011;Bayraktar and Doe, 2013) Fig. S1A,B).…”

“…Besides sharing common proliferation patterns, the Drosophila type II NB lineages mimic many aspects of the less genetically tractable mammalian neural stem cell lineages. Most, if not all, type II NBs produce significant numbers of glia (Viktorin et al, 2011). In addition, apoptosis plays an important role in the shaping of the final pools of type II NB offspring (Jiang and Reichert, 2012).…”

Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster

“…In addition to increased numbers of progeny, type II neuroblasts lineages also show a marked increase in diversity of neural cell types. For example, all type II neuroblasts generate both neurons and glial cell types and are, therefore, in functional terms multipotent neuroglioblasts (Viktorin et al 2011. Moreover, the sub-lineage that each INP generates is composed of markedly different neural types (Wang et al 2014).…”

DrosophilaNeural Stem Cells in Brain Development and Tumor Formation

“…At least two types of glial cells have been shown to have a type II neuroblast origin, namely central complex glia and optic lobe glia. This suggests that type II neuroblasts can be considered as multipotent neuroglial progenitors in the Drosophila brain (Izergina et al, 2009;Viktorin et al, 2011;Viktorin et al, 2013).…”