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

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  • dc.contributor.author Schindler, Magdalena
  • dc.contributor.author Barclay, Alexander
  • dc.contributor.author Marti-Renom, Marc A.
  • dc.contributor.author Real, Francisca M.
  • dc.date.accessioned 2025-10-09T05:49:12Z
  • dc.date.available 2025-10-09T05:49:12Z
  • dc.date.issued 2025
  • dc.description.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.
  • dc.description.sponsorship We thank A. C. Stiege and U. Fischer for their technical support. We thank the Papiliorama Zoo directorate and staff members for their support during sampling. We thank the people from the transgenic and sequencing units from the Max Planck Institute for Molecular Genetics for their assistance. We thank M. Torres for kindly providing us with the MEIS antibodies. We thank all the members from Mundlos, Lupiáñez and Real groups for their fruitful discussions. C.F. was supported by the EMBO Postdoctoral Fellowship ALT 260-2021. S.M. was supported by a grant (GenRevo) from the European Research Council (ERC) and by the grant MU 880/27-1 from the Deutsche Forschungsgemeinschaft. F.M.R. was supported by grants from the Spanish Research Council (RYC2022-035182-I and PID2023-151163NA-I00/MCIN/AEI/10.13039/501100011033). Research in the Lupiañez lab was funded by the ERC (grant no. 101045439, 3D-REVOLUTION) and by the Spanish ‘Agencia Estatal de Investigación’ (grant no. PID2022-143253NB-I00/AEI/10.13039/501100011033/FEDER, UE). Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the ERC Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. R.H. was supported by the ERC (PREVENT, 101078827). This work was supported by the German Research Foundation (grant HI1423/5-1) and the LOEWE-Centre for Translational Biodiversity Genomics (TBG) funded by the Hessen State Ministry of Higher Education, Research and the Arts (HMWK; LOEWE/1/10/519/03/03.001(0014)/52). M.A.M.-R. acknowledges support from the Spanish Ministry of Science and Innovation (PID2020-115696RB-I00 and PID2023-151484NB-I00) as well as the Catalan government through the AGAUR agency (SGR 01127). A.B. acknowledges support from the Spanish Ministry of Science and Innovation, the State Investigation Agency, and the European Social Fund Plus (PRE2022-101632).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation 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
  • dc.identifier.doi http://dx.doi.org/10.1038/s41559-025-02780-x
  • dc.identifier.issn 2397-334X
  • dc.identifier.uri http://hdl.handle.net/10230/71443
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Ecol Evol. 2025 Sep;9(9):1626-42
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101045439
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2023-151163NA-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-143253NB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101078827
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-115696RB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2023-151484NB-I00
  • dc.rights © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Developmental biology
  • dc.subject.keyword Genetics
  • dc.title Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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