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Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function

Author

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  • Marie Kmita

    (University of Geneva, Sciences III)

  • Basile Tarchini

    (University of Geneva, Sciences III)

  • Jozsef Zàkàny

    (University of Geneva, Sciences III)

  • Malcolm Logan

    (National Institute for Medical Research)

  • Clifford J. Tabin

    (Harvard Medical School)

  • Denis Duboule

    (University of Geneva, Sciences III)

Abstract

Vertebrate HoxA and HoxD cluster genes are required for proper limb development1,2,3. However, early lethality, compensation and redundancy have made a full assessment of their function difficult3,4,5. Here we describe mice that are lacking all Hoxa and Hoxd functions in their forelimbs. We show that such limbs are arrested early in their developmental patterning and display severe truncations of distal elements, partly owing to the absence of Sonic hedgehog expression. These results indicate that the evolutionary recruitment of Hox gene function into growing appendages might have been crucial in implementing hedgehog signalling, subsequently leading to the distal extension of tetrapod appendages. Accordingly, these mutant limbs may be reminiscent of an ancestral trunk extension, related to that proposed for arthropods6.

Suggested Citation

  • Marie Kmita & Basile Tarchini & Jozsef Zàkàny & Malcolm Logan & Clifford J. Tabin & Denis Duboule, 2005. "Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function," Nature, Nature, vol. 435(7045), pages 1113-1116, June.
    • Handle: RePEc:nat:nature:v:435:y:2005:i:7045:d:10.1038_nature03648
    DOI: 10.1038/nature03648
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    Cited by:

    1. Marta Losa & Iros Barozzi & Marco Osterwalder & Viviana Hermosilla-Aguayo & Angela Morabito & Brandon H. Chacón & Peyman Zarrineh & Ausra Girdziusaite & Jean Denis Benazet & Jianjian Zhu & Susan Macke, 2023. "A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Naoko Koyano-Nakagawa & Wuming Gong & Satyabrata Das & Joshua W. M. Theisen & Tran B. Swanholm & Daniel Ly & Nikita Dsouza & Bhairab N. Singh & Hiroko Kawakami & Samantha Young & Katherine Q. Chen & Y, 2022. "Etv2 regulates enhancer chromatin status to initiate Shh expression in the limb bud," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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