Center for Developmental Genetics, Department of Biology, College of Arts and Science, New York University, New York, United States.
Elife. 2018 Feb 6;7:e29656. doi: 10.7554/eLife.29656.
In embryos, multipotent progenitors divide to produce distinct progeny and express their full potential. In vertebrates, multipotent cardiopharyngeal progenitors produce second-heart-field-derived cardiomyocytes, and branchiomeric skeletal head muscles. However, the mechanisms underlying these early fate choices remain largely elusive. The tunicate emerged as an attractive model to study early cardiopharyngeal development at high resolution: through two asymmetric and oriented divisions, defined cardiopharyngeal progenitors produce distinct first and second heart precursors, and pharyngeal muscle (aka atrial siphon muscle, ASM) precursors. Here, we demonstrate that differential FGF-MAPK signaling distinguishes between heart and ASM precursors. We characterize a feed-forward circuit that promotes the successive activations of essential ASM determinants, , and . Finally, we show that coupling FGF-MAPK restriction and cardiopharyngeal network deployment with cell divisions defines the timing of gene expression and permits the emergence of diverse cell types from multipotent progenitors.
在胚胎中,多能祖细胞分裂产生不同的后代,并发挥其全部潜能。在脊椎动物中,多能心咽祖细胞产生第二心区源性心肌细胞和鳃弓骨骼头部肌肉。然而,这些早期命运选择的机制在很大程度上仍然难以捉摸。被囊动物作为研究早期心咽发育的高分辨率的有吸引力的模型出现:通过两次不对称和定向分裂,定义的心咽祖细胞产生不同的第一和第二心脏前体以及咽肌(又称心房虹吸管肌肉,ASM)前体。在这里,我们证明了差异的 FGF-MAPK 信号区分心脏和 ASM 前体。我们描述了一个正反馈回路,该回路促进了必需的 ASM 决定因素 、 、 和 的连续激活。最后,我们表明,将 FGF-MAPK 限制和心咽网络部署与细胞分裂相结合,定义了基因表达的时间,并允许多能祖细胞产生不同的细胞类型。