Tornini Valerie A, Puliafito Alberto, Slota Leslie A, Thompson John D, Nachtrab Gregory, Kaushik Anna-Lila, Kapsimali Marika, Primo Luca, Di Talia Stefano, Poss Kenneth D
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin 10060, Italy.
Curr Biol. 2016 Nov 21;26(22):2981-2991. doi: 10.1016/j.cub.2016.08.072. Epub 2016 Nov 10.
The blastema is a mass of progenitor cells that enables regeneration of amputated salamander limbs or fish fins. Methodology to label and track blastemal cell progeny has been deficient, restricting our understanding of appendage regeneration. Here, we created a system for clonal analysis and quantitative imaging of hundreds of blastemal cells and their respective progeny in living adult zebrafish undergoing fin regeneration. Amputation stimulates resident cells within a limited recruitment zone to reset proximodistal (PD) positional information and assemble the blastema. Within the newly formed blastema, the spatial coordinates of connective tissue progenitors are predictive of their ultimate contributions to regenerated skeletal structures, indicating early development of an approximate PD pre-pattern. Calcineurin regulates size recovery by controlling the average number of progeny divisions without disrupting this pre-pattern. Our longitudinal clonal analyses of regenerating zebrafish fins provide evidence that connective tissue progenitors are rapidly organized into a scalable blueprint of lost structures.
芽基是一群祖细胞,能够使蝾螈肢体或鱼鳍再生。标记和追踪芽基细胞后代的方法一直存在缺陷,限制了我们对附肢再生的理解。在此,我们创建了一个系统,用于对数百个芽基细胞及其在成年斑马鱼鳍再生过程中的各自后代进行克隆分析和定量成像。截肢刺激有限募集区内的驻留细胞重置近远轴(PD)位置信息并组装芽基。在新形成的芽基中,结缔组织祖细胞的空间坐标可预测它们对再生骨骼结构的最终贡献,这表明早期已形成近似的PD预模式。钙调神经磷酸酶通过控制后代分裂的平均数量来调节大小恢复,而不会破坏这种预模式。我们对斑马鱼鳍再生的纵向克隆分析提供了证据,表明结缔组织祖细胞迅速组织成丢失结构的可扩展蓝图。