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Hypothalamic Cell Type Evolution across Vertebrates

Wu, Y.; Kalakuntla, P.; Goolsby, B. C.; Rosen, Y.; Hayashi, A.; Yang, G.; Chai, C.; Tate, H. M.; Hindmarsh Sten, T.; Nowicki, J.; Sailer, L. L.; Song, J. H.; Lee, J.; Jones, R. C.; Kim, D.-W.; Kabelik, D.; Ophir, A. G.; Zeng, H.; Leskovec, J.; Quake, S. R.; O'Connell, L. A.; Wang, B.; Luo, L.

2026-08-26 evolutionary biology
10.64898/2026.08.23.746350 bioRxiv
Show abstract

The hypothalamus regulates vital functions and is highly conserved among vertebrates occupying diverse niches, but little is known about the evolution of its cell types. Using comparative single-cell transcriptomics across major vertebrate classes, we identified deeply conserved and clade-specific cell types. While homologous cell types express conserved transcription factors and neuropeptides, their regulatory linkages are often rewired across evolution. The paraventricular nucleus largely retains its neuropeptide expression and responds to dehydration with fine cellular resolution from amphibians to mammals, whereas lamina terminalis neurons are specific to terrestrial vertebrates and exhibit gene expression divergence in cell types activated by dehydration and heat. We propose that a conserved set of keystone cell types sustain essential functions across vertebrates, while flexible gene regulatory programs alongside numerous clade-specific cell types offer evolutionary fluidity.

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