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. [Display omitted] •Filopodia show differential binding affinity in distinct cardioblast subtypes•Adhesion molecules Fas3 and Ten-m have differential expression in cardioblasts•Fas3 differential expression regulates filopodia binding affinity and cell matching•Fas3 and Ten-m display functional redundancy to ensure robust cell matching How selective cell-cell connections in complex multicellular systems are achieved has been a longstanding and important question. Zhang et al. utilize the Drosophila heart as a simplified matching system to demonstrate that differential expression of adhesion molecules directly regulates selective filopodia binding dynamics and therefore instructs robust cell matching.