Sdf1/Cxcr4 signaling controls the dorsal migration of endodermal cells during zebrafish gastrulation
Sdf1/Cxcr4 signaling controls the dorsal migration of endodermal cells during zebrafish gastrulation
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DOI：
10.1242/dev.020107
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发表时间：
2008-08-01
期刊：
影响因子：
4.6
通讯作者：
Kikuchi, Yutaka
中科院分区：
文献类型：
--
作者：
Mizoguchi, Takamasa;Verkade, Heather;Kikuchi, Yutaka
在脊椎动物原肠胚形成期间，中胚层和内胚层细胞都通过外胚层下方的囊胚孔内化。在斑马鱼中，内化的中胚层细胞向原肠胚的背侧移动，同时，它们通过会聚和延伸（C&E）运动向前延伸。显示特征性丝状伪足的内胚层细胞随后迁移到卵黄合胞体层（YSL）附近的下胚层内的内层。然而，很少有人知道内胚层细胞的运动是如何调节原肠胚形成。在这里，我们表明，sdf 1a和sdf 1b表达中胚层细胞控制的cxcr 4a表达内胚层细胞的运动。在原肠胚形成过程中，内胚层细胞的定向迁移受到cxcr 4a或sdf 1a/sdf 1b（sdf 1）基因敲低的抑制。我们还表明，错误表达的Sdf 1作为趋化因子cxcr 4a表达的内胚层细胞。我们进一步发现，使用内胚层特异性转基因品系Tg（sox 17：EGFP），Sdf 1/Cxcr 4信号传导调节内胚层细胞中丝状伪足过程的形成和取向。此外，在内胚层细胞的丝状伪足中没有观察到磷酸肌醇3，4，5-三磷酸（PIP（3））的积累，已知这种积累发生在迁移细胞的前缘。基于我们的研究结果，我们提出，sdf 1表达中胚层细胞，覆盖内胚层层，引导cxcr 4a表达内胚层细胞的背侧的胚胎原肠胚形成过程中，可能通过PIP 3独立的途径。
During vertebrate gastrulation, both mesodermal and endodermal cells internalize through the blastopore beneath the ectoderm. In zebrafish, the internalized mesodermal cells move towards the dorsal side of the gastrula and, at the same time, they extend anteriorly by convergence and extension (C&E) movements. Endodermal cells showing characteristic filopodia then migrate into the inner layer within the hypoblast next to the yolk syncytial layer (YSL). However, little is known about how the movement of endodermal cells is regulated during gastrulation. Here we show that sdf1a- and sdf1b-expressing mesodermal cells control the movements of the cxcr4a-expressing endodermal cells. The directional migration of endodermal cells during gastrulation is inhibited by knockdown of either cxcr4a or sdf1a/sdf1b (sdf1). We also show that misexpressed Sdf1 acts as a chemoattractant for cxcr4a-expressing endodermal cells. We further found, using the endoderm-specific transgenic line Tg(sox17: EGFP), that Sdf1/Cxcr4 signaling regulates both the formation and orientation of filopodial processes in endodermal cells. Moreover, the accumulation of phosphoinositide 3,4,5- trisphosphate (PIP(3)), which is known to occur at the leading edge of migrating cells, is not observed at the filopodia of endodermal cells. Based on our results, we propose that sdf1-expressing mesodermal cells, which overlie the endodermal layer, guide the cxcr4a-expressing endodermal cells to the dorsal side of the embryo during gastrulation, possibly through a PIP3-independent pathway.