| First Author | Pennimpede T | Year | 2012 |
| Journal | Dev Biol | Volume | 372 |
| Issue | 1 | Pages | 55-67 |
| PubMed ID | 22995555 | Mgi Jnum | J:190628 |
| Mgi Id | MGI:5449315 | Doi | 10.1016/j.ydbio.2012.09.003 |
| Citation | Pennimpede T, et al. (2012) In vivo knockdown of Brachyury results in skeletal defects and urorectal malformations resembling caudal regression syndrome. Dev Biol 372(1):55-67 |
| abstractText | 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. |
