Lee Antonio S J, Yoon Nara, Gould Maree, Zhang Ming
Anatomy Department, University of Otago, Dunedin, New Zealand.
Int J Dev Biol. 2018;62(4-5):303-310. doi: 10.1387/ijdb.170116mg.
Formation of an organ is governed by both the genetic programming of individual cells and dynamic interactions amongst different cell communities or the 'community effect'. Using the developing vertebrate limb muscle, we identified myogenic stem cell communities derived from migratory somitic cells. These cells express Pax3, a gene from the paired box (PAX) family of transcription factors and Pax7, a paralog of Pax3. Both Pax genes act upstream of myogenic regulatory factor (MRF) whose activation marks a specified myogenic lineage and subsequent differentiation. Quantitative analyses on the size of the individual cell populations revealed that Pax3 and MRF compartments remained constant. Further analysis showed that the size of the Pax7 cell population increased significantly. The pool of foetal MRF populations contained decreasing Pax3 and increasing Pax7 proportions. This increase is dynamic at the developmental stage. Upon abrupt disruption of the p38 regulatory pathway for myogenic differentiation, established kinetic patterns were significantly altered. Changes in the proportions of these myogenic subpopulations imply that a community effect involving dynamic interactions among differentiating cell communities may play a crucial role in correct maintenance and propagation of myogenic stem cells.
器官的形成受单个细胞的基因编程以及不同细胞群落之间的动态相互作用(即“群落效应”)的共同调控。利用发育中的脊椎动物肢体肌肉,我们鉴定出了源自迁移性体节细胞的生肌干细胞群落。这些细胞表达Pax3(一种来自配对盒(PAX)转录因子家族的基因)和Pax7(Pax3的旁系同源基因)。这两个Pax基因均在生肌调节因子(MRF)的上游起作用,MRF的激活标志着特定的生肌谱系及随后的分化。对各个细胞群体大小的定量分析表明,Pax3和MRF区室保持恒定。进一步分析显示,Pax7细胞群体的大小显著增加。胎儿MRF群体中Pax3的比例下降,Pax7的比例上升。这种增加在发育阶段是动态的。在生肌分化的p38调节途径突然中断后,已建立的动力学模式发生了显著改变。这些生肌亚群比例的变化表明,涉及分化细胞群落之间动态相互作用的群落效应可能在生肌干细胞的正确维持和增殖中起关键作用。