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Tgfbr1 controls developmental plasticity between the hindlimb and external genitalia by remodeling their regulatory landscape

Author

Listed:
  • Anastasiia Lozovska

    (Rua da Quinta Grande 6)

  • Artemis G. Korovesi

    (Rua da Quinta Grande 6)

  • André Dias

    (Rua da Quinta Grande 6
    Universitat Pompeu Fabra)

  • Alexandre Lopes

    (Rua da Quinta Grande 6)

  • Donald A. Fowler

    (Rua da Quinta Grande 6)

  • Gabriel G. Martins

    (Rua da Quinta Grande 6)

  • Ana Nóvoa

    (Rua da Quinta Grande 6)

  • Moisés Mallo

    (Rua da Quinta Grande 6)

Abstract

The hindlimb and external genitalia of present-day tetrapods are thought to derive from an ancestral common primordium that evolved to generate a wide diversity of structures adapted for efficient locomotion and mating in the ecological niche occupied by the species. We show that despite long evolutionary distance from the ancestral condition, the early primordium of the mouse external genitalia preserved the capacity to take hindlimb fates. In the absence of Tgfbr1, the pericloacal mesoderm generates an extra pair of hindlimbs at the expense of the external genitalia. It has been shown that the hindlimb and the genital primordia share many of their key regulatory factors. Tgfbr1 controls the response to those factors by modulating the accessibility status of regulatory elements that control the gene regulatory networks leading to the formation of genital or hindlimb structures. Our work uncovers a remarkable tissue plasticity with potential implications in the evolution of the hindlimb/genital area of tetrapods, and identifies an additional mechanism for Tgfbr1 activity that might also contribute to the control of other physiological or pathological processes.

Suggested Citation

  • Anastasiia Lozovska & Artemis G. Korovesi & André Dias & Alexandre Lopes & Donald A. Fowler & Gabriel G. Martins & Ana Nóvoa & Moisés Mallo, 2024. "Tgfbr1 controls developmental plasticity between the hindlimb and external genitalia by remodeling their regulatory landscape," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46870-z
    DOI: 10.1038/s41467-024-46870-z
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    References listed on IDEAS

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    1. Liang Liang & Changchang Cao & Lei Ji & Zhaokui Cai & Di Wang & Rong Ye & Juan Chen & Xiaohua Yu & Jie Zhou & Zhibo Bai & Ruoyan Wang & Xianguang Yang & Ping Zhu & Yuanchao Xue, 2023. "Complementary Alu sequences mediate enhancer–promoter selectivity," Nature, Nature, vol. 619(7971), pages 868-875, July.
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    1. Jin Ming & Lihui Lin & Jiajun Li & Linlin Wu & Shicai Fang & Tao Huang & Yu Fu & Dong Liu & Wenhui Zhang & Chen Li & Yongzheng Yang & Yi Huang & Yue Qin & Junqi Kuang & Xingnan Huang & Liman Guo & Xia, 2024. "Cell fate decision by a morphogen-transcription factor-chromatin modifier axis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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