Max Planck Institute for Molecular Genetics, Developmental Genetics Department, Ihnestraße 73, 14195 Berlin, Germany.
Dev Biol. 2012 Dec 1;372(1):55-67. doi: 10.1016/j.ydbio.2012.09.003. Epub 2012 Sep 18.
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.
T -box 转录因子 BRACHYURY（T）是胚胎早期发育中中胚层形成的关键调节因子。完全缺失 T 已被证明会导致 E10.0 左右的胚胎致死。在这里，我们描述了一种可诱导的基于 microRNA 的 T 体内敲低小鼠模型，称为 KD3-T，它表现出低等位基因表型。KD3-T 胚胎表现出轴性骨骼缺陷，这是由轴旁中胚层的细胞凋亡引起的，伴随着类似鼠类尿直肠尾综合征和人类尾退化综合征表型的尿直肠畸形。我们表明，KD3-T 胚胎的脊索中 T 的减少导致脊索分化受损及其随后的丧失，而尾部芽中 T 的水平足以延长和模式化轴。此外，KD3-T 胚胎的脊索采用神经特征并丧失作为信号中心的能力。由于 KD3-T 动物存活到出生，它们可用于研究 T 在尿直肠组织发育中的后期作用。
