Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis
Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis
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DOI：
10.1073/pnas.1815063116
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发表时间：
2019-03-05
影响因子：
11.1
通讯作者：
Sawai, Satoshi
中科院分区：
文献类型：
--
作者：
Fujimori, Taihei;Nakajima, Akihiko;Sawai, Satoshi
尽管它们在多细胞组织中发挥着核心作用，但决定细胞重排的导航规则在很大程度上仍然不确定。相邻细胞之间的接触和扩散性吸引分子是组织水平图案化的两个主要决定因素;然而，在大多数情况下，分子和发育的复杂性阻碍了人们对单个细胞运动的确切控制规则进行解码。一个原始的例子，组织图案的细胞重排被发现在社会阿米巴Dictyosteelium discoideum的组织中心或“尖端”的自我组织作为分类的结果分化prestalk和prepore细胞。通过在单细胞水平上采用微流体和基于微球的导航线索操纵，我们发现了一种以前被忽视的盘基网柄菌细胞迁移模式，该模式严格由细胞间接触指导。细胞-细胞接触信号由含有E-set Ig样结构域的异嗜性粘附分子TgrB 1/TgrC 1介导，其反式作用以诱导SCAR复合物的质膜募集和树突状肌动蛋白网络的形成，并且所得的细胞突起与化学引诱物cAMP诱导的突起竞争。此外，我们表明，前柄和前孢子细胞可以突出的接触信号，以及对cAMP的chemotax;然而，当这两个信号，前柄细胞朝向趋化剂，而前孢子细胞选择的接触信号。这些数据表明，细胞分选的模型，通过竞争的阿曲他克林和扩散的线索，每一个有可能驱动自己的集体细胞迁移的模式。
Despite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain largely undefined. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning; however, in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoeba Dictyostelium discoideum where the organizing center or the "tip" self-organizes as a result of sorting of differentiating prestalk and prespore cells. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode of Dictyostelium cell migration that is strictly directed by cell-cell contact. The cell-cell contact signal is mediated by E-set Ig-like domain-containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of the SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude toward the contact signal as well as to chemotax toward cAMP; however, when given both signals, prestalk cells orient toward the chemoattractant, whereas prespore cells choose the contact signal. These data suggest a model of cell sorting by competing juxtacrine and diffusive cues, each with potential to drive its own mode of collective cell migration.