Tornini Valerie A, Thompson John D, Allen Raymond L, Poss Kenneth D
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Regeneration Next, Duke University, Durham, NC 27710, USA.
Development. 2017 Aug 15;144(16):2889-2895. doi: 10.1242/dev.155655.
The blastema is a mass of progenitor cells responsible for regeneration of amputated salamander limbs and fish fins. Previous studies have indicated that resident cell sources producing the blastema contribute lineage-restricted progeny to regenerating tissue. However, these studies have labeled general cell types rather than granular cell subpopulations, and they do not explain the developmental transitions that must occur for distal structures to arise from cells with proximal identities in the appendage stump. Here, we find that regulatory sequences of , which encodes an enzyme that synthesizes serotonin, mark a subpopulation of fibroblast-like cells restricted to the joints of uninjured adult zebrafish fins. Amputation stimulates serotonin production in regenerating fin fibroblasts, yet targeted mutations abrogating this response do not disrupt fin regeneration. In uninjured animals, -expressing cells contribute fibroblast progeny that remain restricted to joints throughout life. By contrast, upon amputation, joint cells give rise to fibroblasts that distribute across the entire lengths of regenerating fin rays. Our experiments visualize and quantify how incorporation into an appendage blastema broadens the progeny contributions of a cellular subpopulation that normally has proximodistal restrictions.
芽基是一群祖细胞,负责蝾螈肢体和鱼鳍断肢的再生。先前的研究表明,产生芽基的驻留细胞源会为再生组织贡献谱系受限的后代。然而,这些研究标记的是一般细胞类型而非颗粒细胞亚群,并且它们没有解释从附肢残端具有近端身份的细胞产生远端结构所必须发生的发育转变。在这里,我们发现编码一种合成血清素的酶的基因的调控序列标记了一类成纤维细胞样细胞亚群,该亚群仅限于未受伤的成年斑马鱼鳍的关节。截肢刺激再生鳍成纤维细胞中血清素的产生,但消除这种反应的靶向突变不会破坏鳍的再生。在未受伤的动物中,表达该基因的细胞贡献的成纤维细胞后代终生都局限于关节。相比之下,截肢后,关节细胞产生的成纤维细胞会分布在再生鳍条的整个长度上。我们的实验可视化并量化了并入附肢芽基如何拓宽通常具有近端到远端限制的细胞亚群的后代贡献。