Wnt- and glutamate-receptors orchestrate stem cell dynamics and asymmetric cell division.

Sergi Junyent,Tung-Jui Trieu,Joshua C Reeves,Jethro Lundie-Brown,Shukry J Habib,Clare L Garcin,James La Szczerkowski,Matthew Wilson

doi:10.7554/elife.59791

Abstract

The Wnt-pathway is part of a signalling network that regulates many aspects of cell biology. Recently, we discovered crosstalk between AMPA/Kainate-type ionotropic glutamate receptors (iGluRs) and the Wnt-pathway during the initial Wnt3a-interaction at the cytonemes of mouse embryonic stem cells (ESCs). Here, we demonstrate that this crosstalk persists throughout the Wnt3a-response in ESCs. Both AMPA and Kainate receptors regulate early Wnt3a-recruitment, dynamics on the cell membrane, and orientation of the spindle towards a Wnt3a-source at mitosis. AMPA receptors specifically are required for segregating cell fate components during Wnt3a-mediated asymmetric cell division (ACD). Using Wnt-pathway component knockout lines, we determine that Wnt co-receptor Lrp6 has particular functionality over Lrp5 in cytoneme formation, and in facilitating ACD. Both Lrp5 and 6, alongside pathway effector β-catenin act in concert to mediate the positioning of the dynamic interaction with, and spindle orientation to, a localised Wnt3a-source. Wnt-iGluR crosstalk may prove pervasive throughout embryonic and adult stem cell signalling.

Highlights

Cell to cell communication is fundamental to multicellular life
Recently we discovered crosstalk between AMPA/Kainate-type ionotropic glutamate receptors and the Wnt-pathway during the initial Wnt3a-interaction at the cytonemes of mouse embryonic stem cells (ESCs)
We show that AMPA/Kainate-type ionotropic glutamate receptors (iGluRs) activity is incorporated throughout 90 the interaction of ESCs with localized Wnt3a signals

Summary

Introduction

Cell to cell communication is fundamental to multicellular life. Developmental signals critical for tissue patterning and formation are traditionally considered as diffuse signals that pervade the extracellular matrix. Signals have often been found to be delivered to target cells or received from source cells via specialized signalling filopodia — cytonemes 32 (Kornberg and Roy, 2014). Stem cells, both embryonic and adult, regulate tissue formation. In several systems (Bertrand, 2016; Goldstein et al, 2006; Huang and Niehrs, 2014; Kaur et al, 2020; Sugioka et al, 2011; Walston et al, 2004), including mouse embryonic stem cells (ESCs) (Habib et al, 2013), localized Wnts induce oriented asymmetric cell division (ACD)

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