A pre-vertebrate endodermal origin of calcitonin-producing neuroendocrine cells

Rees, J. M.; Kirk, K.; Gattoni, G.; Hockman, D.; Ritter, D. J.; Benito Gutierrez, E.; Knapik, E.; Crump, J. G.; Fabian, P.; Gillis, J. A.

doi:10.1101/2024.02.17.580846

bioRxiv · 10.1101/2024.02.17.580846

A pre-vertebrate endodermal origin of calcitonin-producing neuroendocrine cells

Rees, J. M.·Kirk, K.·Gattoni, G.·Hockman, D.·Ritter, D. J.·Benito Gutierrez, E.·Knapik, E.·Crump, J. G.·Fabian, P.·Gillis, J. A.

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Abstract

Vertebrate calcitonin-producing cells (C-cells) are neuroendocrine cells that secrete the small peptide hormone calcitonin in response to elevated blood calcium levels. C-cells are crucial for maintenance of calcium homeostasis, yet the embryonic and evolutionary origins of this cell type remain contentious. Whereas mouse C-cells reside within the thyroid gland and derive from pharyngeal endoderm, avian C-cells are located within ultimobranchial glands and were reported to derive from the neural crest. We use a comparative cell lineage tracing approach in a range of vertebrate model systems to resolve the ancestral embryonic origin of vertebrate C-cells. We find, contrary to previous studies, that chick C-cells derive from pharyngeal endoderm, with neural crest-derived cells instead contributing to connective tissue intimately associated with C-cells in the ultimobranchial gland. This endodermal origin of C-cells is conserved in a ray-finned bony fish (zebrafish) and a cartilaginous fish (the little skate, Leucoraja erinacea). Furthermore, we discover putative C-cell homologues within the endodermally-derived pharyngeal epithelium of the ascidian Ciona intestinalis and the amphioxus Branchiostoma lanceolatum, two invertebrate chordates that lack neural crest cells. Our findings point to a conserved endodermal origin of C-cells across vertebrates and to a pre-vertebrate origin of this cell type along the chordate stem.

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Rees, J. M., Kirk, K., Gattoni, G., Hockman, D., Ritter, D. J., Benito Gutierrez, E., Knapik, E., Crump, J. G., Fabian, P., Gillis, J. A.. 2024-02-21. A pre-vertebrate endodermal origin of calcitonin-producing neuroendocrine cells. https://doi.org/10.1101/2024.02.17.580846

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