Control of planar divisions by the G-protein regulator LGN maintains progenitors in the chick neuroepithelium

Abstract

The spatio-temporal regulation of symmetrical as opposed to asymmetric cell divisions directs the fate and location of cells in the developing CNS. In invertebrates, G-protein regulators control spindle orientation in asymmetric divisions, which generate progeny with different identities. We investigated the role of the G-protein regulator LGN (also called Gpsm2) in spindle orientation and cell-fate determination in the spinal cord neuroepithelium of the developing chick embryo. We show that LGN is located at the cell cortex and spindle poles of neural progenitors, and that it regulates spindle movements and orientation. LGN promotes planar divisions in the early spinal cord. Interfering with LGN function randomizes the plane of division. Notably, this does not affect cell fate, but frequently leads one daughter of proliferative symmetric divisions to exit the neuroepithelium prematurely and to proliferate aberrantly in the mantle zone. Hence, tight control of planar spindle orientation maintains neural progenitors in the neuroepithelium, and regulates the proper development of the nervous system.

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

“…In both the spinal cord and cerebral cortex, as in the majority of DT divisions, LGN localizes to lateral domains, where LGN loss increases oblique/perpendicular divisions, suggesting that LGN normally promotes planar divisions (Morin et al, 2007;Konno et al, 2008;Peyre et al, 2011;Shitamukai et al, 2011). However, in epidermis, we and others have shown that LGN forms an apical complex with Insc, Gαi3, NuMA, dynactin and Par3 and that LGN loss leads to loss of perpendicular divisions, impaired Notch signaling and lethal defects in epidermal barrier formation and differentiation (Lechler and Fuchs, 2005;Poulson and Lechler, 2010;Williams et al, 2011Williams et al, , 2014.…”

Assessing the Role of the Cadherin/Catenin Complex at the Schwann Cell–Axon Interface and in the Initiation of Myelination

“…Additionally, during asymmetric cell division, Par-3 recruits proteins such as Inscuteable, which in turn recruits Partner of Inscuteable (Pins) (Cai et al, 2003;Siller et al, 2006). Pins directly associates with heterotrimeric G-protein subunits and microtubuleassociated proteins to dictate the orientation of the microtubules and their positioning along the cell cortex (Izumi et al, 2006;Siller et al, 2006;Morin et al, 2007;Konno et al, 2008). Could redundant mechanisms exist in the SC, whereby Par-3 recruits microtubule-associated proteins to position and orient microtubules so that polymerization may lead to elongation, membrane spreading, and/or proper positioning of the SC as ensheathment initiates?…”

Drosophila neuroblasts: a model for stem cell biology

“…Ags3-null mice show no defects in brain morphology or function (Blumer et al, 2008). By contrast, knocking out Lgn randomizes the orientation of normally planar neuroepithelial divisions, consistent with it having a role in mitotic spindle orientation in the developing brain (Morin et al, 2007;Konno et al, 2008). The mammalian Mud homolog NuMA (a nuclear protein that associates with the mitotic apparatus; Numa1 -Mouse Genome Informatics) has a role in the establishment and maintenance of spindle poles (Sun and Schatten, 2006;Silk et al, 2009).…”