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

Abstract

Glial cells form part of the neural stem cell niche and express a wide variety of ion channels; however, the contribution of these channels to nervous system development is poorly understood. We explored the function of the Drosophila ClC‐a chloride channel, since its mammalian ortholog CLCN2 is expressed in glial cells, and defective channel function results in leukodystrophies, which in humans are accompanied by cognitive impairment. We found that ClC‐a was expressed in the niche in cortex glia, which are closely associated with neurogenic tissues. Characterization of loss‐of‐function ClC‐a mutants revealed that these animals had smaller brains and widespread wiring defects. We showed that ClC‐a is required in cortex glia for neurogenesis in neuroepithelia and neuroblasts, and identified defects in a neuroblast lineage that generates guidepost glial cells essential for photoreceptor axon guidance. We propose that glia‐mediated ionic homeostasis could nonautonomously affect neurogenesis, and consequently, the correct assembly of neural circuits.

Slit/Robo Signaling Regulates Multiple Stages of the Development of the Drosophila Motion Detection System

“…Next, we analyzed the expression of Slit ligand using a previously described slit:GFP line [ sli MI03825–GFSTF.2 , ( Caipo et al, 2020 ; Plazaola-Sasieta et al, 2019 ; Venken et al, 2011 )]. We found that Slit was expressed in populations of glial cells that surround the p-IPC neuroepithelium and migratory progenitors (see arrowheads and arrow in Supplementary Figures 2G–I′″ ).…”

A Rare Novel CLCN2 Variation and Risk of Gilles de la Tourette Syndrome: Whole-Exome Sequencing in a Multiplex Family and a Follow-Up Study in a Chinese Population

“…CLCN2 encodes chloride channel 2 (CLC-2), which is a type of permeable chloride channel that belongs to the family of CLCN2 channel/transport proteins ( 13 ). CLCN2 is expressed in glia precursors during development and is required for their differentiation into astrocytes and oligodendrocytes ( 14 , 15 ). Mutations in CLCN2 are responsible for leukoencephalopathy with ataxia ( 16 ).…”

Neuron–glia interaction in the Drosophila nervous system

“…In addition, these glial cells control neuroblast proliferation (Coutinho-Budd et al, 2017;Read, 2018;Spéder & Brand, 2018). The effect on neurogenesis requires the chloride channel ClC-a which is expressed by the cortex glia (Plazaola Sasieta et al, 2019) and possibly the SLC7 amino acid transporter Sobremesa (Sbm) (Galagovsky et al, 2018). Sbm is expressed in cortex glia and the subperineurial glia (see below).…”