eLife (May 2021)

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

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

DOI
https://doi.org/10.7554/eLife.59791
Journal volume & issue
Vol. 10

Abstract

Read online

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.

Keywords