Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development

Schindler, Magdalena; Barclay, Alexander; Marti-Renom, Marc A.; Real, Francisca M.

doi:http://dx.doi.org/10.1038/s41559-025-02780-x

Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development

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Schindler M, Feregrino C, Aldrovandi S, Lo BW, Monaco AA, Ringel AR, et al. Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development. Nat Ecol Evol. 2025 Sep;9(9):1626-42. DOI: 10.1038/s41559-025-02780-x

Abstract

Bats are the only mammals capable of self-powered flight, an evolutionary innovation based on the transformation of forelimbs into wings. The bat wing is characterized by an extreme elongation of the second to fifth digits with a wing membrane called the chiropatagium connecting them. Here we investigated the developmental and cellular origin of this structure by comparing bat and mouse limbs using omics tools and single-cell analyses. Despite the substantial morphological differences between the species, we observed an overall conservation of cell populations and gene expression patterns including interdigital apoptosis. Single-cell analyses of micro-dissected embryonic chiropatagium identified a specific fibroblast population, independent of apoptosis-associated interdigital cells, as the origin of this tissue. These distal cells express a conserved gene programme including the transcription factors MEIS2 and TBX3, which are commonly known to specify and pattern the early proximal limb. Transgenic ectopic expression of MEIS2 and TBX3 in mouse distal limb cells resulted in the activation of genes expressed during wing development and phenotypic changes related to wing morphology, such as the fusion of digits. Our results elucidate fundamental molecular mechanisms of bat wing development and illustrate how drastic morphological changes can be achieved through repurposing of existing developmental programmes during evolution.