The LGN protein promotes planar proliferative divisions in the neocortex but apicobasal asymmetric terminal divisions in the retina.

Document Type

Article

Publication Date

2-15-2016

Keywords

Animals, Asymmetric Cell Division, COS Cells, Carrier Proteins, Cell Proliferation, Cercopithecus aethiops, GTP-Binding Protein alpha Subunits, Gi-Go, Mice, Neocortex, Retina, Stem Cells

JAX Source

Development 2016 Feb 15; 143(4):575-81

Volume

143

Issue

4

First Page

575

Last Page

581

ISSN

1477-9129

PMID

26755700

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. Development 2016 Feb 15; 143(4):575-81.

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