Glycogen Synthase Kinase 3 regulates the genesis of displaced retinal ganglion cells - Sorbonne Université Access content directly
Journal Articles eNeuro Year : 2021

Glycogen Synthase Kinase 3 regulates the genesis of displaced retinal ganglion cells

Abstract

Glycogen Synthase Kinase 3 (GSK) 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 morphological defects. A single wild-type allele of either Gsk3α or Gsk3β is able to rescue this phenotype. In this genetic context, all cell types are present with a functional retina. However, we unexpectedly detect 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 of Gsk3α is expressed. Excess dRGCs lead to 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 in Gsk3 mutant 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.Significance StatementGlycogen Synthase Kinase 3 (GSK) proteins (Gsk3α or Gsk3β) are key mediators of signaling pathways, especially in the central nervous system but poorly described in the retina. Here we show that the complete loss of GSK3 in mouse retinal progenitors leads to microphthalmia. However, when only one allele of Gsk3α or Gsk3β are present, all cell types are present with a functional retina. More importantly, we unexpectedly uncover a unique role of GSK3 in controlling the genesis of retinal ganglion cells in the inner nuclear layer which could correspond to a rare and poorly characterized retinal cell type. Therefore, our mouse models potentially offer a unique and powerful model system to study the visual function of dRGCs in mammals.
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Dates and versions

hal-03354295 , version 1 (24-09-2021)

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Elena Kisseleff, Robin J Vigouroux, Catherine Hottin, Sophie Lourdel, Leah Thomas, et al.. Glycogen Synthase Kinase 3 regulates the genesis of displaced retinal ganglion cells. eNeuro, 2021, 8 (3), pp.ENEURO.0171-21.2021. ⟨10.1523/ENEURO.0171-21.2021⟩. ⟨hal-03354295⟩
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