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Dev Biol. 2012 Dec 1;372(1):55-67. doi: 10.1016/j.ydbio.2012.09.003. Epub 2012 Sep 18.

In vivo knockdown of Brachyury results in skeletal defects and urorectal malformations resembling caudal regression syndrome.

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Max Planck Institute for Molecular Genetics, Developmental Genetics Department, Ihnestraße 73, 14195 Berlin, Germany.


The T-box transcription factor BRACHYURY (T) is a key regulator of mesoderm formation during early development. Complete loss of T has been shown to lead to embryonic lethality around E10.0. Here we characterize an inducible miRNA-based in vivo knockdown mouse model of T, termed KD3-T, which exhibits a hypomorphic phenotype. KD3-T embryos display axial skeletal defects caused by apoptosis of paraxial mesoderm, which is accompanied by urorectal malformations resembling the murine uro-recto-caudal syndrome and human caudal regression syndrome phenotypes. We show that there is a reduction of T in the notochord of KD3-T embryos which results in impaired notochord differentiation and its subsequent loss, whereas levels of T in the tailbud are sufficient for axis extension and patterning. Furthermore, the notochord in KD3-T embryos adopts a neural character and loses its ability to act as a signaling center. Since KD3-T animals survive until birth, they are useful for examining later roles for T in the development of urorectal tissues.

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