Selective Filopodia Adhesion Ensures Robust Cell Matching in the Drosophila Heart

The ability to form specific cell-cell connections within complex cellular environments is critical for multicellular organisms. However, the underlying mechanisms of cell matching that instruct these connections remain elusive. Here, we quantitatively explored the dynamics and regulation of cell matching processes utilizing Drosophila cardiogenesis. We found that cell matching is highly robust at boundaries between cardioblast (CB) subtypes, and filopodia of different CB subtypes have distinct binding affinities. Cdc42 is involved in regulating this selective filopodia binding adhesion and influences CB matching. Further, we identified adhesion molecules Fasciclin III (Fas3) and Ten-m, both of which also regulate synaptic targeting, as having complementary differential expression in CBs. Altering Fas3 expression changes differential filopodia adhesion and leads to CB mismatch. Furthermore, only when both Fas3 and Ten-m are lost is CB alignment severely impaired. Our results show that differential adhesion mediated by selective filopodia binding efficiently regulates precise and robust cell matching.