Distinct gene regulatory dynamics drive skeletogenic cell fate convergence during vertebrate embryogenesis

Menghan Wang, Ana Di Pietro-Torres, Christian Feregrino, Maëva Luxey, Chloé Moreau, Sabrina Fischer, Antoine Fages, Danilo Ritz and Patrick Tschopp ()
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Menghan Wang: University of Basel
Ana Di Pietro-Torres: University of Basel
Christian Feregrino: University of Basel
Maëva Luxey: University of Basel
Chloé Moreau: University of Basel
Sabrina Fischer: University of Basel
Antoine Fages: University of Basel
Danilo Ritz: University of Basel
Patrick Tschopp: University of Basel

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Cell type repertoires have expanded extensively in metazoan animals, with some clade-specific cells being crucial to evolutionary success. A prime example are the skeletogenic cells of vertebrates. Depending on anatomical location, these cells originate from three different precursor lineages, yet they converge developmentally towards similar cellular phenotypes. Furthermore, their ‘skeletogenic competency’ arose at distinct evolutionary timepoints, thus questioning to what extent different skeletal body parts rely on truly homologous cell types. Here, we investigate how lineage-specific molecular properties are integrated at the gene regulatory level, to allow for skeletogenic cell fate convergence. Using single-cell functional genomics, we find that distinct transcription factor profiles are inherited from the three precursor states and incorporated at lineage-specific enhancer elements. This lineage-specific regulatory logic suggests that these regionalized skeletogenic cells are distinct cell types, rendering them amenable to individualized selection, to define adaptive morphologies and biomaterial properties in different parts of the vertebrate skeleton.

Date: 2025
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DOI: 10.1038/s41467-025-57480-8

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