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1 Vertebrate organs are arranged in a stereotypic, species-specific position along the animal body 2 plan. Substantial morphological variation exists between related species, especially so in the vastly 3 diversified teleost clade. It is still unclear how tissues, organs and systems can accommodate such 4 diverse scaffolds. Here, we use the sequential formation of neuromasts in the posterior lateral line 5 (pLL) system of medaka fish to address tissue-interactions defining a pattern. We show that the 6 pLL pattern is established independently of its neuronal wiring, and demonstrate that the neuromast 7 precursors that constitute the pLL behave as autonomous units during pattern construction. We 8 uncover the necessity of epithelial integrity for correct pLL patterning by disrupting keratin 15 (krt15) 9 and creating epithelial lesions that lead to novel neuromast positioning. By using krt15/wt chimeras, 10 we determined that the new pLL pattern depends exclusively on the mutant epithelium, which 11 instructs wt neuromast to locate ectopically. Inducing epithelial lesions by 2-photon laser ablation 12 during pLL morphogenesis phenocopies krt15 genetic mutants and reveals that epithelial integrity 13 defines the final position of the embryonic pLL neuromasts. Our results show that a fine-balance 14 between primordium intrinsic properties and instructive interactions with the surrounding tissues is 15 necessary to achieve proper organ morphogenesis and patterning. We speculate that this logic 16 likely facilitates the accommodation of sensory modules to changing and diverse body plans.

Mammals display a species-specific number, size and location of organs exclusively built during embryogenesis. In fish and amphibians, however, organs must adapt to life-long growth either by expanding in size and/or increasing in number. Here we use neuromasts, small sensory organs that increase in number as fish grow in size, to explore organogenesis during post-embryonic stages. Using iterative imaging, we reveal that post-embryonic organogenesis in the medaka caudal-neuromast-cluster (CNC) is mediated by organ-founder stem cells that delaminate from a functional neuromast. Organ-founder stem cells undergo epithelial-to-mesenchymal (EMT) transition as shown by molecular markers and cellular rearrangements. Chemokine signaling controls the dynamics of organ-founder stem cell delamination, which occurs at a stereotypic position that endures experimental and genetic perturbations. 2-photon laser ablation experiments reveal that organ-founder stem cells are rapidly reconstituted and suggest that these do not constitute a pre-defined population but are rather specified in situ. Our findings contribute to better understanding physiological stem-cell mediated organogenesis, a growth strategy present in life-long growing vertebrates. We speculate that a similar strategy could operate in vertebrates with determined-size as a template for pathological conditions like metastasis, where cells detach from their original organ and expand remotely.

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