FGF8 induces chemokinesis and regulates condensation of mouse nephron progenitor cells

• Published in: Development (Cambridge) Vol. 149; no. 21
• Main Authors: Sharma, Abhishek, Meer, Marco, Dapkunas, Arvydas, Ihermann-Hella, Anneliis, Kuure, Satu, Vainio, Seppo J, Iber, Dagmar, Naillat, Florence
• Format: Journal Article
• Language: English
• Published: England 01.11.2022
• Subjects: Animals; Fibroblast Growth Factor 8 - genetics; Fibroblast Growth Factor 8 - metabolism; Fibroblast Growth Factors - metabolism; Kidney - metabolism; Mice; Mice, Transgenic; Nephrons - metabolism; Organogenesis; Stem Cells - metabolism; Computing modelling; Nephron progenitor cells; Condensation step; Kidney development
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.201012

Kidneys develop via iterative branching of the ureteric epithelial tree and subsequent nephrogenesis at the branch points. Nephrons form in the cap mesenchyme as the metanephric mesenchyme (MM) condenses around the epithelial ureteric buds (UBs). Previous work has demonstrated that FGF8 is important for the survival of nephron progenitor cells (NPCs), and early deletion of Fgf8 leads to the cessation of nephron formation, which results in post-natal lethality. We now reveal a previously unreported function of FGF8. By combining transgenic mouse models, quantitative imaging assays and data-driven computational modelling, we show that FGF8 has a strong chemokinetic effect and that this chemokinetic effect is important for the condensation of NPCs to the UB. The computational model shows that the motility must be lower close to the UB to achieve NPC attachment. We conclude that the FGF8 signalling pathway is crucial for the coordination of NPC condensation at the UB. Chemokinetic effects have also been described for other FGFs and may be generally important for the formation of mesenchymal condensates.