Embryology Unit, Children's Medical Research Institute, Sydney, Australia.
Dev Biol. 2012 Feb 15;362(2):132-40. doi: 10.1016/j.ydbio.2011.11.020. Epub 2011 Dec 8.
Development of the mouse forelimb bud depends on normal Twist1 activity. Global loss of Twist1 function before limb bud formation stops limb development and loss of Twist1 throughout the mesenchyme after limb bud initiation leads to polydactyly, the ulnarization or loss of the radius and malformations and reductions of the shoulder girdle. Here we show that conditional deletion of Twist1 by Mesp1-Cre in the mesoderm that migrates into the anterior-proximal part of the forelimb bud results in the development of supernumerary digits and carpals, the acquisition of ulna-like characteristics by the radius and malformations of the humerus and scapula. The mirror-like duplications and posteriorization of pre-axial tissues are preceded by disruptions to anterior-posterior Shh, Bmp and Fgf signaling gradients and dysregulation of transcription factors that regulate anterior-posterior limb patterning.
小鼠前肢芽的发育依赖于 Twist1 功能的正常发挥。在肢芽形成之前，Twist1 功能的全局缺失会阻止肢芽的发育，而在肢芽起始后，Twist1 在间质中的缺失会导致多指畸形、尺骨的桡骨化或丢失以及肩带的畸形和减少。在这里，我们发现通过 Mesp1-Cre 在中胚层中的条件性敲除，该中胚层迁移到前肢芽的前近端部分，导致多余的数字和腕骨的发育，桡骨获得尺骨样特征以及肱骨和肩胛骨的畸形。前轴组织的镜像复制和后移先于前-后 Shh、Bmp 和 Fgf 信号梯度的破坏，以及调节前-后肢模式形成的转录因子的失调。
