Fibroblasts promote osmotic surveillance by wound-induced unique calcium patterns

Fibroblasts are pivotal in tissue homeostasis, contributing to tissue repair and environmental sensing. Studying their role in zebrafish has been hampered by the lack of robust transgene expression tools. Here, we developed a fin fibroblast-specific synthetic promoter by combining the zebrafish itga11a regulatory region with the murine cFos minimal promoter. Establishing this itga11a-cFos promoter in the QF2–QUAS system enabled evaluation of damage-induced signaling pathways in fibroblasts using genetically encoded biosensors. Our findings reveal that fibroblasts generate spatially distinct, sustained calcium signals in response to epithelial injury, in contrast to transient oscillatory signals in keratinocytes. These calcium signals are modulated by external osmotic cues, highlighting a role for fibroblasts in osmotic surveillance. We also show that tissue damage activates the cPla2-mediated shape-sensing and nuclear swelling–dependent pathways in fibroblasts. Our results demonstrate the versatility of the itga11a-cFos promoter in driving fibroblast-specific expression of biosensors and ablation tools. Using this toolkit, we provide new insights into damage-induced signaling pathways in fibroblasts.

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