Dlg1 controls planar spindle orientation in the neuroepithelium through direct interaction with LGN

Author:

Saadaoui Mehdi123,Machicoane Mickaël456,di Pietro Florencia1237,Etoc Fred123,Echard Arnaud45,Morin Xavier123

Affiliation:

1. Institut de Biologie de l’École Normale Supérieure, Ecole Normale Supérieure, F-75005 Paris, France

2. Institut National de la Santé et de la Recherche Medicale, U1024, F-75005 Paris, France

3. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8197, F-75005 Paris, France

4. Membrane Traffic and Cell Division Laboratory, Institut Pasteur, F-75015 Paris, France

5. Centre National de la Recherche Scientifique, Unité de Recherche Associée 2582, F-75015 Paris, France

6. Cellule Pasteur–Université Pierre et Marie Curie, Université Pierre et Marie Curie, F-75015 Paris, France

7. Institute of Doctoral Studies (IFD), Sorbonne Universités, Université Pierre et Marie Curie–Université Paris 6, F-75252 Paris, France

Abstract

Oriented cell divisions are necessary for the development of epithelial structures. Mitotic spindle orientation requires the precise localization of force generators at the cell cortex via the evolutionarily conserved LGN complex. However, polarity cues acting upstream of this complex in vivo in the vertebrate epithelia remain unknown. In this paper, we show that Dlg1 is localized at the basolateral cell cortex during mitosis and is necessary for planar spindle orientation in the chick neuroepithelium. Live imaging revealed that Dlg1 is required for directed spindle movements during metaphase. Mechanistically, we show that direct interaction between Dlg1 and LGN promotes cortical localization of the LGN complex. Furthermore, in human cells dividing on adhesive micropatterns, homogenously localized Dlg1 recruited LGN to the mitotic cortex and was also necessary for proper spindle orientation. We propose that Dlg1 acts primarily to recruit LGN to the cortex and that Dlg1 localization may additionally provide instructive cues for spindle orientation.

Publisher

Rockefeller University Press

Subject

Cell Biology

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