Mechanosensory organ regeneration in zebrafish depends on a population of multipotent progenitor cells kept latent by Schwann cells.
Mechanosensory organ regeneration in zebrafish depends on a population of multipotent progenitor cells kept latent by Schwann cells.
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DOI：
10.1186/s12915-016-0249-2
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发表时间：
2016-04-07
期刊：
影响因子：
5.4
通讯作者：
Allende ML
中科院分区：
文献类型：
--
作者：
Sánchez M;Ceci ML;Gutiérrez D;Anguita-Salinas C;Allende ML
再生受损组织是一个复杂的过程，需要祖细胞，必须刺激祖细胞进行增殖，分化，并经常迁移行为和形态学变化。多种细胞类型，既驻留在受损组织内，又被招募到病变部位，已被证明参与其中。然而，涉及损伤后祖细胞增殖和分化的激活的细胞和分子机制，以及它们由不同细胞类型的调节，尚未完全理解。斑马鱼侧线是一个合适的系统，研究再生，因为它的大部分组成部分是完全恢复后，损坏。后侧线（PLL）是一个机械感觉系统，胚胎发育，最初由7至8个神经瘤组成，分布在沿着躯干和尾巴，由连续条纹的神经间细胞（INC）连接。INCs由于下面的雪旺细胞的存在而保持静止状态。它们在发育过程中被激活，形成中间神经瘤。然而，没有研究描述INCs是否可以参与再生事件，例如，在神经肥大完全丧失后。我们使用电消融在PLL组件中表达荧光蛋白的转基因幼虫中完全消融幼虫和成鱼中的单个神经瘤。这种损伤导致INCs、雪旺氏细胞和PLL神经的不连续性。在体成像显示，INCs填补了损伤后留下的差距，并能在损伤区再生一个新的神经肥大。此外，单个INC能够在再生的神经肥大中分裂并形成所有细胞类型，并且在此过程中，它瞬时表达神经祖细胞标记物sox 2基因。我们证明了雪旺细胞作为INC增殖和神经肥大再生的负调节因子的关键作用，并且这种抑制特性完全依赖于活性ErbB信号传导。损伤后再生神经肥大的潜力需要祖细胞（INC）暂时从附近的雪旺细胞产生的抑制信号中释放出来。这种简单而高效的双组分生态位为动物提供了强大的器官生长和再生机制，可以在整个生命周期中持续。本文的在线版本（doi：10.1186/s12915-016-0249-2）包含补充材料，可供授权用户使用。
Regenerating damaged tissue is a complex process, requiring progenitor cells that must be stimulated to undergo proliferation, differentiation and, often, migratory behaviors and morphological changes. Multiple cell types, both resident within the damaged tissue and recruited to the lesion site, have been shown to participate. However, the cellular and molecular mechanisms involved in the activation of progenitor cell proliferation and differentiation after injury, and their regulation by different cells types, are not fully understood. The zebrafish lateral line is a suitable system to study regeneration because most of its components are fully restored after damage. The posterior lateral line (PLL) is a mechanosensory system that develops embryonically and is initially composed of seven to eight neuromasts distributed along the trunk and tail, connected by a continuous stripe of interneuromastic cells (INCs). The INCs remain in a quiescent state owing to the presence of underlying Schwann cells. They become activated during development to form intercalary neuromasts. However, no studies have described if INCs can participate in a regenerative event, for example, after the total loss of a neuromast. We used electroablation in transgenic larvae expressing fluorescent proteins in PLL components to completely ablate single neuromasts in larvae and adult fish. This injury results in discontinuity of the INCs, Schwann cells, and the PLL nerve. In vivo imaging showed that the INCs fill the gap left after the injury and can regenerate a new neuromast in the injury zone. Further, a single INC is able to divide and form all cell types in a regenerated neuromast and, during this process, it transiently expresses the sox2 gene, a neural progenitor cell marker. We demonstrate a critical role for Schwann cells as negative regulators of INC proliferation and neuromast regeneration, and that this inhibitory property is completely dependent on active ErbB signaling. The potential to regenerate a neuromast after damage requires that progenitor cells (INCs) be temporarily released from an inhibitory signal produced by nearby Schwann cells. This simple yet highly effective two-component niche offers the animal robust mechanisms for organ growth and regeneration, which can be sustained throughout life. The online version of this article (doi:10.1186/s12915-016-0249-2) contains supplementary material, which is available to authorized users.