Regulation of neuroblast proliferation by surface glia in the Drosophila larval brain

Abstract

Despite the importance of precisely regulating stem cell division, the molecular basis for this control is still elusive. Here, we show that surface glia in the developing Drosophila brain play essential roles in regulating the proliferation of neural stem cells, neuroblasts (NBs). We found that two classes of extracellular factors, Dally-like (Dlp), a heparan sulfate proteoglycan, and Glass bottom boat (Gbb), a BMP homologue, are required for proper NB proliferation. Interestingly, Dlp expressed in perineural glia (PG), the most outer layer of the surface glia, is responsible for NB proliferation. Consistent with this finding, functional ablation of PG using a dominant-negative form of dynamin showed that PG has an instructive role in regulating NB proliferation. Gbb acts not only as an autocrine proliferation factor in NBs but also as a paracrine survival signal in the PG. We propose that bidirectional communication between NBs and glia through TGF-β signaling influences mutual development of these two cell types. We also discuss the possibility that PG and NBs communicate via direct membrane contact or transcytotic transport of membrane components. Thus, our study shows that the surface glia acts not only as a simple structural insulator but also a dynamic regulator of brain development.

Drosophila ClC‐a is required in glia of the stem cell niche for proper neurogenesis and wiring of neural circuits

“…Concomitant defects in neuroblast proliferation and photoreceptor targeting have been observed in other studies (González, Romani, Cubas, Modolell, & Campuzano, ; Kanai et al, ; Zhu et al, ), and it has been proposed that the Activin signaling pathway is required to produce the proper number of neurons to enable proper connection of incoming photoreceptor axons to their targets (Zhu et al, ). Interestingly, mutations in the proneural gene asense , which is expressed in type I neuroblasts, GMCs and INPs, has adult targeting phenotypes that are extremely similar to the ones observed in ClC‐a mutants (González et al, ).…”

“…targeting have been observed in other studies (González, Romani, Cubas, Modolell, & Campuzano, 1989;Kanai et al, 2018;Zhu et al, 2008), and it has been proposed that the Activin signaling pathway is Figure 12) was used to visualize the slit expression pattern (red, i'-k'). ClC-a + medulla glia (green, i''-k'') are outlined (white dashed line) in (i-i'', j-j'').…”

“…The cellular components in the fly niche comprise the neurogenic cells themselves (neuroepithelia and/or neuroblasts and precursor cells), the newly generated neurons, and three types of glia. Of these latter, the perineural and subperineural glia are components of the blood brain barrier (BBB) that respond to systemic nutritional cues and signal to neuroblasts to proliferate (Chell & Brand, 2010;Kanai et al, 2018;Perez-Gomez, Slovakova, Rives-Quinto, Krejci, & Carmena, 2013;Sousa-Nunes, Yee, & Gould, 2011;Spéder & Brand, 2014). Cortex glia are large cells that lie beneath the subperineural glia.…”

Drosophila glia: Few cell types and many conserved functions

“…In addition to its blood–brain barrier function, the subperineurial glia also acts as a control element during the reactivation of quiescent neuroblasts in response to nutritional signals ‐ possibly in conjunction with the perineurial glia (Kanai et al, ; Sousa‐Nunes, Yee, & Gould, ; Spéder & Brand, ; Spéder, Liu, & Brand, ). Binding of a so far unknown signal from the fat body will result in secretion of insulin by the subperineurial glia.…”

Waking up quiescent neural stem cells: Molecular mechanisms and implications in neurodevelopmental disorders

“…The TGF-β/BMP (bone morphogenetic protein) pathway plays crucial roles during various cellular processes such as cell growth and differentiation. The BMP signaling pathway promotes NSC proliferation in Drosophila because Glass bottom boat (Gbb), a BMP homolog that is expressed in NSCs, acts as an autocrine proliferation factor in NSCs [81]. Dally-like (Dlp), a heparan sulfate proteoglycan protein on the cell surface and in the extracellular matrix, functions as a coreceptor for Gbb in PG to promote NSC proliferation [81].…”