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

• Published in: eLife Vol. 10
• Main Authors: Junyent, Sergi, Reeves, Joshua C, Szczerkowski, James LA, Garcin, Clare L, Trieu, Tung-Jui, Wilson, Matthew, Lundie-Brown, Jethro, Habib, Shukry J
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 24.05.2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; asymmetric cell division; beta Catenin - genetics; beta Catenin - metabolism; Cell Biology; Cell Differentiation; Cell Division; Cell fate; Cell Line; Cell Lineage; Cell membranes; Cloning; cytonemes; Embryo cells; Embryonic stem cells; Genes; Glutamate; glutamate receptors; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Kainic acid receptors; Ligands; Low Density Lipoprotein Receptor-Related Protein-5 - genetics; Low Density Lipoprotein Receptor-Related Protein-5 - metabolism; Low Density Lipoprotein Receptor-Related Protein-6 - genetics; Low Density Lipoprotein Receptor-Related Protein-6 - metabolism; LRP5 protein; Mice; Microscopy, Confocal; Microscopy, Fluorescence; Microscopy, Video; Mitosis; Mouse Embryonic Stem Cells - metabolism; Receptor Cross-Talk; Receptors, AMPA - genetics; Receptors, AMPA - metabolism; Receptors, Kainic Acid - genetics; Receptors, Kainic Acid - metabolism; Signal transduction; spindle orientation; stem cell; Stem cell transplantation; Stem cells; Stem Cells and Regenerative Medicine; Time Factors; Wnt protein; Wnt Signaling Pathway; Wnt signalling; Wnt3A Protein - genetics; Wnt3A Protein - metabolism; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; β-Catenin; Fiji; asymmetric cell division; mouse; stem cells; Wnt signalling; cell biology; stem cell; regenerative medicine; cytonemes; spindle orientation; glutamate receptors
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.59791

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.