1. Drosophila ClC‐a is required in glia of the stem cell niche for proper neurogenesis and wiring of neural circuits
- Author
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Haritz Plazaola-Sasieta, Martín Ríos, Marta Morey, Qi Zhu, Raúl Estévez, and Héctor Gaitán-Peñas
- Subjects
0301 basic medicine ,Nervous system ,glia ,Stem cells ,Animals, Genetically Modified ,0302 clinical medicine ,Neural Stem Cells ,Loss of Function Mutation ,Drosophila Proteins ,ClC-a chloride channel ,BRAIN ,Research Articles ,GENE-EXPRESSION ,Cerebral Cortex ,axon guidance ,Teixit nerviós ,Malalties neurodegeneratives ,Neurogenesis ,PROLIFERATION ,Neurodegenerative Diseases ,ClC‐a chloride channel ,Neural stem cell ,Cell biology ,neurogenesis ,medicine.anatomical_structure ,Neurology ,Chloride channel ,Drosophila ,neural circuit assembly ,Cèl·lules mare ,Life Sciences & Biomedicine ,Neuroglia ,RADIAL GLIA ,Research Article ,RETINAL AXONS ,Biology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Neuroblast ,Chloride Channels ,ION CHANNELS ,medicine ,Biological neural network ,Animals ,stem cell niche ,Nerve tissue ,Science & Technology ,urogenital system ,SENSORINEURAL DEAFNESS ,CHLORIDE CHANNELS ,Neurosciences ,VISUAL-SYSTEM ,Cortex (botany) ,030104 developmental biology ,nervous system ,Axon guidance ,Neurosciences & Neurology ,NEURONAL EXCITABILITY ,Nerve Net ,030217 neurology & neurosurgery - 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., Main Points ClC‐a chloride channel is expressed in glia of the stem cell niche and regulates neurogenesis in a non‐autonomous fashion. ClC‐a mutants have reduced neurogenesis, and consequently, smaller brains.ClC‐a mutants also display wiring defects.
- Published
- 2019
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