PT  - JOURNAL ARTICLE
AU  - Elena Kisseleff
AU  - Robin J. Vigouroux
AU  - Catherine Hottin
AU  - Sophie Lourdel
AU  - Leah Thomas
AU  - Parth Shah
AU  - Alain Chédotal
AU  - Muriel Perron
AU  - Anand Swaroop
AU  - Jerome E. Roger
TI  - Glycogen Synthase Kinase 3 Regulates the Genesis of Displaced Retinal Ganglion Cells3
AID  - 10.1523/ENEURO.0171-21.2021
DP  - 2021 Sep 01
TA  - eneuro
PG  - ENEURO.0171-21.2021
VI  - 8
IP  - 5
4099  - http://www.eneuro.org/content/8/5/ENEURO.0171-21.2021.short
4100  - http://www.eneuro.org/content/8/5/ENEURO.0171-21.2021.full
SO  - eNeuro2021 Sep 01; 8
AB  - 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 either Gsk3α or Gsk3β is 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 of Gsk3α is 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 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.