Anatomical integration of the sacral-hindlimb unit coordinated by GDF11 underlies variation in hindlimb positioning in tetrapods

Yoshiyuki Matsubara, Tatsuya Hirasawa, Shiro Egawa, Ayumi Hattori, Takaya Suganuma, Yuhei Kohara, Tatsuya Nagai, Koji Tamura, Shigeru Kuratani, Atsushi Kuroiwa, Takayuki Suzuki

    Research output: Contribution to journalArticlepeer-review

    25 Citations (Scopus)


    Elucidating how body parts from different primordia are integrated during development is essential for understanding the nature of morphological evolution. In tetrapod evolution, while the position of the hindlimb has diversified along with the vertebral formula, the mechanism responsible for this coordination has not been well understood. However, this synchronization suggests the presence of an evolutionarily conserved developmental mechanism that coordinates the positioning of the hindlimb skeleton derived from the lateral plate mesoderm with that of the sacral vertebrae derived from the somites. Here we show that GDF11 secreted from the posterior axial mesoderm is a key factor in the integration of sacral vertebrae and hindlimb positioning by inducing Hox gene expression in two different primordia. Manipulating the onset of GDF11 activity altered the position of the hindlimb in chicken embryos, indicating that the onset of Gdf11 expression is responsible for the coordinated positioning of the sacral vertebrae and hindlimbs. Through comparative analysis with other vertebrate embryos, we also show that each tetrapod species has a unique onset timing of Gdf11 expression, which is tightly correlated with the anteroposterior levels of the hindlimb bud. We conclude that the evolutionary diversity of hindlimb positioning resulted from heterochronic shifts in Gdf11 expression, which led to coordinated shifts in the sacral-hindlimb unit along the anteroposterior axis.

    Original languageEnglish
    Pages (from-to)1392-1399
    Number of pages8
    JournalNature Ecology and Evolution
    Issue number9
    Publication statusPublished - 2017 Sept 1

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Ecology


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