Center for Developmental Genetics, Department of Biology, New York University, New York, NY 10003, USA.
Center for Developmental Genetics, Department of Biology, New York University, New York, NY 10003, USA; Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, USA; Courant Institute of Mathematical Sciences, New York University, New York, NY 10012, USA.
Dev Cell. 2014 May 12;29(3):263-76. doi: 10.1016/j.devcel.2014.04.001. Epub 2014 May 1.
In vertebrates, pluripotent pharyngeal mesoderm progenitors produce the cardiac precursors of the second heart field as well as the branchiomeric head muscles and associated stem cells. However, the mechanisms underlying the transition from multipotent progenitors to distinct muscle precursors remain obscured by the complexity of vertebrate embryos. Using Ciona intestinalis as a simple chordate model, we show that bipotent cardiopharyngeal progenitors are primed to activate both heart and pharyngeal muscle transcriptional programs, which progressively become restricted to corresponding precursors. The transcription factor COE (Collier/OLF/EBF) orchestrates the transition to pharyngeal muscle fate both by promoting an MRF-associated myogenic program in myoblasts and by maintaining an undifferentiated state in their sister cells through Notch-mediated lateral inhibition. The latter are stem cell-like muscle precursors that form most of the juvenile pharyngeal muscles. We discuss the implications of our findings for the development and evolution of the chordate cardiopharyngeal mesoderm.
在脊椎动物中，多能咽中胚层祖细胞产生第二心脏场的心脏前体细胞以及鳃弓头部肌肉和相关的干细胞。然而，由脊椎动物胚胎的复杂性所掩盖，多能祖细胞向不同的肌肉前体细胞的转变的机制仍然不清楚。我们使用海鞘作为一个简单的脊索动物模型，表明双能心咽祖细胞已经准备好激活心脏和咽肌肉的转录程序，这些程序逐渐局限于相应的前体细胞。转录因子 COE（Collier/OLF/EBF）通过在成肌细胞中促进与 MRF 相关的肌生成程序，并通过 Notch 介导的侧抑制作用在其姐妹细胞中维持未分化状态，来协调向咽肌肉命运的转变。后者是类似干细胞的肌肉前体细胞，形成了大部分的幼体咽肌肉。我们讨论了我们的发现对脊索动物心咽中胚层发育和进化的意义。
