Migration of Kupffer's vesicle derived cells is essential for tail morphogenesis in zebrafish embryos

A phenotypic screen of fungal filtrates on developing zebrafish embryos identified metabolites from the fungus Ceratocystis populicola to induce ectopic tail formation, including a split notochord and a duplicated caudal fin. Chemical analyses led to the identification of monoterpene alcohols, in particular geraniol, as the active compounds. Tüpfel long fin (TL) zebrafish embryos were more susceptible to geraniol-induced ectopic tail formation than Wild Indian Karyotpe (WIK) zebrafish embryos. RNA sequencing on tail buds of 15-somite stage embryos revealed downregulation of essential genes of the retinoic acid signaling pathway. Differential expression of cyp26a1, fgf8a and downstream hox-genes was validated. Time-lapse imaging revealed that Kupffer's vesicle derived cells failed to migrate after Kupffer's vesicle collapse upon geraniol treatment. These cells failed to merge with progenitors from the tail bud and contributed to an ectopic tail, expressing markers for presomitic mesoderm, somite and notochord tissue. Strikingly, ablation of Kupffer's vesicle by tbxta-morpholino injection rescued ectopic tail formation. Taken together, our data suggests that Kupffer's vesicle cells harbor tail progenitor capacity, and proper migration of these cells is essential for normal tail morphogenesis.