Luminal signalling links cell communication to tissue architecture during organogenesis
Luminal signalling links cell communication to tissue architecture during organogenesis
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DOI：
10.1038/nature13852
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发表时间：
2014-11-06
期刊：
影响因子：
64.8
通讯作者：
Gilmour, Darren
中科院分区：
文献类型：
--
作者：
Durdu, Sevi;Iskar, Murat;Gilmour, Darren
形态发生是细胞集体形成分化的组织和器官的过程(1)。最近的研究证明了形态发生的自组织性质，表明三维培养的干细胞可以产生复杂的类器官，如迷你肠道(2)、光学杯(3)甚至迷你大脑(4)。为了实现这一点，细胞集体必须调节控制细胞分化的分泌信号分子的活动，可能是通过微环境或生态位的自组装。然而，允许组织结构变化直接反馈细胞外信号活动的机制尚未被描述。在这里，我们研究了组织组装过程如何控制体内器官发生过程中的信号活动，使用迁移的斑马鱼侧线原基(5)。我们发现，组织内的成纤维细胞生长因子（FGF）活性控制着它沉积玫瑰状机械感觉器官的频率。实时成像显示FGF特别集中在聚集在这些器官中心的微腔结构中，并在空间上限制其信号活动。基因抑制微腔组装和激光微穿刺实验表明，微腔增加了参与细胞的信号反应，从而允许FGF协调组织后部细胞群的迁移行为。由于中央管腔的形成是许多细胞类型(如上皮细胞（6)和胚胎干细胞(7)）的自组织特性，因此管腔信号传导提供了一种潜在的通用机制，可以局部限制、协调和增强组织内的细胞通信。
Morphogenesis is the process whereby cell collectives are shaped into differentiated tissues and organs(1). The self-organizing nature of morphogenesis has been recently demonstrated by studies showing that stem cells in three-dimensional culture can generate complex organoids, such as mini-guts(2), optic-cups(3) and even mini-brains(4). To achieve this, cell collectives must regulate the activity of secreted signalling molecules that control cell differentiation, presumably through the self-assembly of microenvironments or niches. However, mechanisms that allow changes in tissue architecture to feedback directly on the activity of extracellular signals have not been described. Here we investigate how the process of tissue assembly controls signalling activity during organogenesis in vivo, using the migrating zebrafish lateral line primordium(5). We show that fibroblast growth factor (FGF) activity within the tissue controls the frequency at which it deposits rosette-like mechanosensory organs. Live imaging reveals that FGF becomes specifically concentrated in microluminal structures that assemble at the centre of these organs and spatially constrain its signalling activity. Genetic inhibition of microlumen assembly and laser micropuncture experiments demonstrate that microlumina increase signalling responses in participating cells, thus allowing FGF to coordinate the migratory behaviour of cell groups at the tissue rear. As the formation of a central lumen is a self-organizing property of many cell types, such as epithelia(6) and embryonic stem cells(7), luminal signalling provides a potentially general mechanism to locally restrict, coordinate and enhance cell communication within tissues.