Ephrin-Eph signalling drives the asymmetric division of notochord/neural precursors in Ciona embryos
Ephrin-Eph signalling drives the asymmetric division of notochord/neural precursors in Ciona embryos
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DOI：
10.1242/dev.003939
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发表时间：
2007-04-15
期刊：
影响因子：
4.6
通讯作者：
Yasuo, Hitoyoshi
中科院分区：
文献类型：
--
作者：
Picco, Vincent;Hudson, Clare;Yasuo, Hitoyoshi
细胞不对称分裂产生两个命运截然不同的同胞细胞，为发育中的胚胎提供了一种产生细胞多样性的重要手段。已经描述了许多这样的细胞分裂的例子，但到目前为止，只有有限数量的潜在机制被阐明。在这里，我们发现了一种控制海鞘胚胎细胞不对称分裂的新机制。这种分裂产生一个脊索和一个神经前体。胞外信号调节激酶(ERK)在兄弟细胞之间的不同激活决定了它们不同的命运，ERK的激活促进了脊索的命运。我们首先证明了脊索和神经命运的分离是母细胞的自主属性，母细胞通过与邻近的外胚层前体相互作用获得这种功能极性。我们发现，这些细胞间的相互作用是由ePhin-Eph信号系统介导的，该信号系统先前被认为参与控制细胞的移动和黏附。中断与信号细胞的接触或抑制EPhin-Eph信号会导致母细胞的对称分裂，产生两个脊索前体。最后，我们证明了ePhin-Eph信号通过减弱神经命运子细胞中ERK的激活而起作用。我们提出了一个模型，通过这个模型，定向的ePhin-Eph信号在功能上极化脊索/神经母细胞，导致子细胞之间的成纤维细胞生长因子-RAS-ERK通路的不对称调制，从而决定它们的不同命运。
Asymmetric cell divisions produce two sibling cells with distinct fates, providing an important means of generating cell diversity in developing embryos. Many examples of such cell divisions have been described, but so far only a limited number of the underlying mechanisms have been elucidated. Here, we have uncovered a novel mechanism controlling an asymmetric cell division in the ascidian embryo. This division produces one notochord and one neural precursor. Differential activation of extracellular-signal-regulated kinase (ERK) between the sibling cells determines their distinct fates, with ERK activation promoting notochord fate. We first demonstrate that the segregation of notochord and neural fates is an autonomous property of the mother cell and that the mother cell acquires this functional polarity via interactions with neighbouring ectoderm precursors. We show that these cellular interactions are mediated by the ephrin-Eph signalling system, previously implicated in controlling cell movement and adhesion. Disruption of contacts with the signalling cells or inhibition of the ephrin-Eph signal results in the symmetric division of the mother cell, generating two notochord precursors. Finally, we demonstrate that the ephrin-Eph signal acts via attenuation of ERK activation in the neural-fated daughter cell. We propose a model whereby directional ephrin-Eph signals functionally polarise the notochord/neural mother cell, leading to asymmetric modulation of the FGF-Ras-ERK pathway between the daughter cells and, thus, to their differential fate specification.