Local Dkk1 Crosstalk from Breeding Ornaments Impedes Regeneration of Injured Male Zebrafish Fins

• Male zebrafish use pectoral fin epidermal tubercles (ETs) for spawning
• Male pectoral fin ET cells vigorously renew through Wnt activation and inhibition
• Wnt inhibitor Dkk1 produced by ET interferes with signaling during fin regeneration
• A paradigm for the loss of tissue regenerative capacity during species evolution

SummaryPrecise spatiotemporal regulation of signaling activators and inhibitors can help limit developmental crosstalk between neighboring tissues during morphogenesis, homeostasis, and regeneration. Here, we find that the secreted Wnt inhibitor Dkk1b is abundantly produced by dense regions of androgen-regulated epidermal tubercles (ETs) on the surfaces of adult male zebrafish pectoral fins. High-speed videos and amputation experiments reveal that pectoral fins and their ETs are used for male spawning. Formation and vigorous turnover of ETs involve Dkk1b induction and maintenance, whereas Dkk1b is typically restricted from the regeneration blastema after an amputation injury. When amputation occurs through a region containing ETs, a Dkk1b-enriched wound epidermis forms and blastema formation is disrupted, compromising regeneration. Thus, homeostatic signaling by key breeding ornaments can interfere with injury-activated tissue regeneration. Our findings help explain sexually dimorphic fin regeneration in zebrafish and have implications for how regenerative potential might decline as development progresses or during species evolution.

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