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bioRxiv · 10.1101/2020.06.16.154609

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

Habib, S.·Junyent, S.·Reeves, J. C.·Szczerkowski, J. L. A.·Garcin, C. L.·Trieu, T.-J.·Wilson, M.
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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 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 {beta}-catenin act in concert to mediate the positioning of the dynamic interaction with, and spindle orientation to, a localized Wnt3a-source. Wnt-iGluR crosstalk may prove pervasive throughout embryonic and adult stem cell signalling.

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Habib, S., Junyent, S., Reeves, J. C., Szczerkowski, J. L. A., Garcin, C. L., Trieu, T.-J., Wilson, M.. 2020-06-16. Wnt-and Glutamate-receptors orchestrate stem cell dynamics and asymmetric cell division. https://doi.org/10.1101/2020.06.16.154609

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