title: The LGN protein promotes planar proliferative divisions in the neocortex but apicobasal asymmetric terminal divisions in the retina.
abstract: Cell division orientation is crucial to control segregation of polarized fate determinants in the daughter cells to produce symmetric or asymmetric fate outcomes. Most studies in vertebrates have focused on the role of mitotic spindle orientation in proliferative asymmetric divisions and it remains unclear whether altering spindle orientation is required for the production of asymmetric fates in differentiative terminal divisions. Here, we show that the GoLoco motif protein LGN, which interacts with Gαi to control apicobasal division orientation in Drosophila neuroblasts, is excluded from the apical domain of retinal progenitors undergoing planar divisions, but not in those undergoing apicobasal divisions. Inactivation of LGN reduces the number of apicobasal divisions in mouse retinal progenitors, whereas it conversely increases these divisions in cortical progenitors. Although LGN inactivation increases the number of progenitors outside the ventricular zone in the developing neocortex, it has no effect on the position or number of progenitors in the retina. Retinal progenitor cell lineage analysis in LGN mutant mice, however, shows an increase in symmetric terminal divisions producing two photoreceptors, at the expense of asymmetric terminal divisions producing a photoreceptor and a bipolar or amacrine cell. Similarly, inactivating Gαi decreases asymmetric terminal divisions, suggesting that LGN function with Gαi to control division orientation in retinal progenitors. Together, these results show a context-dependent function for LGN and indicate that apicobasal divisions are not involved in proliferative asymmetric divisions in the mouse retina, but are instead essential to generate binary fates at terminal divisions.
authors.affiliation: Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montréal (IRCM), Montreal, Québec, Canada H2W 1R7.
authors.forename: Marine
authors.initials: M
authors.lastname: Lacomme
authors.affiliation: Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montréal (IRCM), Montreal, Québec, Canada H2W 1R7.
authors.forename: Basile
authors.initials: B
authors.lastname: Tarchini
authors.affiliation: Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montréal (IRCM), Montreal, Québec, Canada H2W 1R7 Integrated Program in Neuroscience, McGill University, Montreal, Québec, Canada H3A 2B4.
authors.forename: Camille
authors.initials: C
authors.lastname: Boudreau-Pinsonneault
authors.affiliation: Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montréal (IRCM), Montreal, Québec, Canada H2W 1R7.
authors.forename: Carine
authors.initials: C
authors.lastname: Monat
authors.affiliation: Cellular Neurobiology Research Unit, Institut de recherches cliniques de Montréal (IRCM), Montreal, Québec, Canada H2W 1R7 Integrated Program in Neuroscience, McGill University, Montreal, Québec, Canada H3A 2B4 Department of Medicine, Université de Montréal, Montreal, Québec, Canada H3T 1J4 Department of Anatomy and Cell Biology, and Division of Experimental Medicine, McGill University, Montreal, Québec, Canada H3A 0G4 michel.cayouette@ircm.qc.ca.
authors.forename: Michel
authors.initials: M
authors.lastname: Cayouette
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D051379:Mice; D019579:Neocortex / Q000166:cytology*; D012160:Retina / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C579276:Gnai1 protein, mouse; C502655:LGN protein, mouse; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: Asymmetric cell division; Cell fate decision; Cell lineage; Differentiation; Oriented divisions; Retina; Self-renewal; Stem cell