Molecular basis of cell migration in the fish lateral line:: Role of the chemokine receptor CXCR4 and of its ligand, SDF1
Molecular basis of cell migration in the fish lateral line:: Role of the chemokine receptor CXCR4 and of its ligand, SDF1
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DOI：
10.1073/pnas.252339399
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发表时间：
2002-12-10
影响因子：
11.1
通讯作者：
Ghysen, A
中科院分区：
文献类型：
--
作者：
David, NB;Sapède, D;Ghysen, A
细胞迁移在许多形态发生过程中起着至关重要的作用，其失调有许多戏剧性的后果。然而，在正常发展期间如何控制移徙仍然是一个基本上没有解决的问题。我们研究了这一过程的情况下，后侧线（PLL），存在于鱼类和两栖动物的mechanosensory系统。在斑马鱼中，胚胎PLL包括7至8个沿着动物的侧腹从头部到尾部排列的感觉器官（神经乳突），并且由起源于头部基板的原基形成。这个原基沿着沿着一条固定的路径向尾尖迁移，并在尾尖沉积离散的细胞群，每个细胞群都将成为神经肥大。我们发现，SDF 1样趋化因子的踪迹是存在沿着的途径的原基和CXCR 4样趋化因子受体表达的迁移细胞。配体或其受体的失活阻断了迁移，而在正常SDF 1踪迹不存在的突变体中，原基路径被重定向到下一个更腹侧的SDF 1表达结构域。在所有情况下，感觉轴突仍然与原基相关联，表明神经突的延伸以形成PLL神经取决于原基的运动。我们的结论是，该系统的形成和神经支配依赖于SDF 1-CXCR 4系统，这也被牵连在人类的几个迁移事件，包括转移形成和淋巴细胞归巢。
Cell migration plays an essential role in many morphogenetic processes, and its deregulation has many dramatic consequences. Yet how migration is controlled during normal development is still a largely unresolved question. We examined this process in the case of the posterior lateral line (PLL), a mechanosensory system present in fish and amphibians. In zebrafish, the embryonic PLL comprises seven to eight sense organs (neuromasts) aligned from head to tail along the flank of the animal and is formed by a primordium that originates from a cephalic placode. This primordium migrates along a stereotyped pathway toward the tip of the tail and deposits in its wake discrete groups of cells, each of which will become a neuromast. We show that a trail of SDF1-like chemokine is present along the pathway of the primordium and that a CXCR4-like chemokine receptor is expressed by the migrating cells. The inactivation of either the ligand or its receptor blocks migration, whereas in mutants in which the normal SDF1 trail is absent, the primordium path is redirected to the next, more ventral sdf1 expression domain. In all cases, the sensory axons remain associated to the primordium, indicating that the extension of the neurites to form the PLL nerve depends on the movement of the primordium. We conclude that both the formation and the innervation of this system depend on the SDF1-CXCR4 system, which has also been implicated in several migration events in humans, including metastasis formation and lymphocyte homing.