Organ-Founder Stem Cells Mediate Post-Embryonic Neuromast Formation In Medaka

Abstract

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.