ErbB expressing Schwann cells control lateral line progenitor cells via non-cell-autonomous regulation of Wnt/β-catenin.
ErbB expressing Schwann cells control lateral line progenitor cells via non-cell-autonomous regulation of Wnt/β-catenin.
复制标题
DOI：
10.7554/elife.01832
复制
发表时间：
2014-03-18
期刊：
影响因子：
7.7
通讯作者：
Piotrowski T
中科院分区：
文献类型：
--
作者：
Lush ME;Piotrowski T
祖细胞的静止和激活的正确协调在胚胎发育和成人体内平衡过程中至关重要。我们利用斑马鱼的感觉侧线来定义生态位-祖细胞相互作用，以了解不同信号通路在空间和时间上的整合如何调节这些过程的协调。我们之前的研究表明雪旺细胞在负调节侧线祖细胞增殖中发挥着至关重要的作用。在这里，我们证明 ErbB/神经调节蛋白信号传导不仅是施万细胞迁移所必需的，而且它在迁移后的施万细胞中持续发挥作用。表达 ErbB 的雪旺细胞通过非细胞自主抑制 Wnt/β-连环蛋白信号传导来抑制侧系祖细胞增殖和分化。 Fgf 信号的后续激活控制感觉器官分化，但不控制祖细胞增殖。除了侧线之外，这些发现对于理解生态位祖细胞在发育过程中如何分离相互作用以及它们在疾病状态下如何出错具有重要意义。 DOI：http://dx.doi.org/10.7554/eLife.01832.001 构成动物身体的所有不同类型的细胞都源自单个受精卵。当卵子发育成胚胎时，细胞分裂并专门形成特定类型的细胞，例如：肝细胞、肌肉细胞或神经细胞。胚胎中注定成为特定细胞类型的细胞称为祖细胞。然而，这些细胞也存在于成体组织中，它们在那里等待，直到需要它们来替换旧的或受损的细胞。斑马鱼常用于科学研究，与其他鱼类一样，它们有一条沿着身体两侧延伸的“侧线”，其中包含检测周围水域运动的细胞。在其发育过程中，侧线包含许多祖细胞，这些祖细胞准备形成更多的这些感觉器官。侧线还连接到神经细胞，将有关水运动的信息传递到中枢神经系统，而其他称为雪旺细胞的细胞则支持神经细胞。众所周知，雪旺细胞创造的局部环境或“生态位”可以防止侧线内的祖细胞过早变成其特定的细胞类型。然而，导致祖细胞停止分裂、随后重新开始分裂并转变为预定细胞类型的分子尚不清楚。现在，Lush 和 Piotrowski 发现，通过一种名为 ErbB 的蛋白质发出的信号会导致雪旺细胞增殖，但对侧线附近的祖细胞会产生相反的效果。雪旺细胞中的 ErbB 信号传导抑制祖细胞中的多种信号传导途径；虽然其中一些途径通常会促进祖细胞繁殖，但另一些途径则会导致它们转变为特定的细胞类型。 Lush 和 Piotrowski 的发现对于理解祖细胞与其周围细胞之间的相互作用如何影响其发育具有重要意义。这些发现可能有助于理解细胞增殖控制或细胞类型变化出错时引起的疾病，例如发育异常或癌症。 DOI：http://dx.doi.org/10.7554/eLife.01832.002
Proper orchestration of quiescence and activation of progenitor cells is crucial during embryonic development and adult homeostasis. We took advantage of the zebrafish sensory lateral line to define niche-progenitor interactions to understand how integration of diverse signaling pathways spatially and temporally regulates the coordination of these processes. Our previous studies demonstrated that Schwann cells play a crucial role in negatively regulating lateral line progenitor proliferation. Here we demonstrate that ErbB/Neuregulin signaling is not only required for Schwann cell migration but that it plays a continued role in postmigratory Schwann cells. ErbB expressing Schwann cells inhibit lateral line progenitor proliferation and differentiation through non-cell-autonomous inhibition of Wnt/β-catenin signaling. Subsequent activation of Fgf signaling controls sensory organ differentiation, but not progenitor proliferation. In addition to the lateral line, these findings have important implications for understanding how niche-progenitor cells segregate interactions during development, and how they may go wrong in disease states. DOI: http://dx.doi.org/10.7554/eLife.01832.001 All the different types of cells that make up the body of an animal are descended from a single fertilized egg. As this egg develops into an embryo, the cells divide and specialize to become a specific type of cell, such as: a liver cell, a muscle cell or a nerve cell. The cells in the embryo that are destined to become specific cell types are called progenitor cells. However, these cells are also found within adult tissues, where they wait until they are needed to replace old or damaged cells. Zebrafish are commonly used in scientific research and, like other fish, they have a ‘lateral line’ that runs along both sides of the body and contains cells that detect movements in the surrounding water. During its development, the lateral line contains many progenitors that are primed to form more of these sense organs. The lateral line is also connected to nerve cells that relay information about water movements to the central nervous system, while other cells called Schwann cells support the nerve cells. The local environment or ‘niche’ created by the Schwann cells is known to prevent the progenitor cells within the lateral line from becoming their specific cell type too early. However, the molecules that cause progenitor cells to stop dividing, and later restart dividing and change in to their predestined cell type is not well understood. Now Lush and Piotrowski have discovered that signaling through a protein called ErbB causes the Schwann cells to multiply, but has the opposite effect on nearby progenitor cells in the lateral line. ErbB signaling in the Schwann cells inhibited various signaling pathways in the progenitor cells; and whilst some of these pathways normally encourage the progenitors to multiply, others cause them to change into their specific cell type. The findings of Lush and Piotrowski have important implications for understanding how the interactions between progenitor cells and the cells around them affect their development. These findings may be useful for understanding diseases caused when the control of cell multiplication or cell-type changes goes awry—such as developmental abnormalities or cancer. DOI: http://dx.doi.org/10.7554/eLife.01832.002