Glycogen Synthase Kinase 3 Regulates the Genesis of Displaced Retinal Ganglion Cells3
| Autor: | Jerome E. Roger, Parth Shah, Muriel Perron, Anand Swaroop, Sophie Lourdel, Catherine Hottin, Elena Kisseleff, Leah Thomas, Robin J. Vigouroux, Alain Chédotal |
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| Rok vydání: | 2021 |
| Předmět: |
Retinal Ganglion Cells
Biology Retinal ganglion Retina Mice chemistry.chemical_compound GSK-3 post-translational modifications medicine Animals retinal development General Neuroscience displaced ganglion cells Retinal General Medicine glycogen synthase kinase 3 Axons Cell biology cell death medicine.anatomical_structure chemistry Retinal ganglion cell medial terminal nucleus Inner nuclear layer Optomotor response Sensory and Motor Systems sense organs Neural development Research Article: New Research |
| Zdroj: | eNeuro |
| ISSN: | 2373-2822 |
| DOI: | 10.1523/eneuro.0171-21.2021 |
| Popis: | Glycogen synthase kinase 3 (GSK3) proteins (GSK3α and GSK3β) are key mediators of signaling pathways, with crucial roles in coordinating fundamental biological processes during neural development. Here we show that the complete loss of GSK3 signaling in mouse retinal progenitors leads to microphthalmia with broad morphologic defects. A single wild-type allele of eitherGsk3αorGsk3βis able to rescue this phenotype. In this genetic context, all cell types are present in a functional retina. However, we unexpectedly detected a large number of cells in the inner nuclear layer expressing retinal ganglion cell (RGC)-specific markers (called displaced RGCs, dRGCs) when at least one allele ofGsk3αis expressed. The excess of dRGCs leads to an increased number of axons projecting into the ipsilateral medial terminal nucleus, an area of the brain belonging to the non-image-forming visual circuit and poorly targeted by RGCs in wild-type retina. Transcriptome analysis and optomotor response assay suggest that at least a subset of dRGCs inGsk3mutant mice are direction-selective RGCs. Our study thus uncovers a unique role of GSK3 in controlling the production of ganglion cells in the inner nuclear layer, which correspond to dRGCs, a rare and poorly characterized retinal cell type. |
| Databáze: | OpenAIRE |
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