Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo
Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo
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DOI：
10.1101/gad.13.14.1834
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发表时间：
1999-07-15
影响因子：
10.5
通讯作者：
Martin, GR
中科院分区：
文献类型：
--
作者：
Sun, X;Meyers, EN;Martin, GR
Fgf8和Fgf4编码成纤维细胞生长因子（FGF）家族成员，它们在原肠胚形成期的小鼠胚胎原条中共同表达。我们分析了Fgf8（-/-）胚胎的表型，发现它们在原条中无法表达Fgf4。在缺乏FGF8和FGF4两者的情况下，上胚层细胞进入原条并经历上皮 - 间充质转化，但大多数细胞随后无法从原条迁移离开。结果是，尽管形成了胚外组织，但没有胚胎中胚层或内胚层衍生的组织发育。在突变胚胎中，预期神经外胚层的模式形成受到极大干扰。前神经外胚层标记物广泛表达，至少部分是因为在没有定形内胚层的情况下，提供调节其表达信号的前脏壁内胚层不会向近端移位。后神经外胚层标记物不表达，大概是因为在预期神经外胚层下方既没有中内胚层，也没有形态正常的结来提供其表达所必需的诱导信号。这项研究确定Fgf8是原肠胚形成所必需的基因，并表明通过FGF8和/或FGF4的信号传导是细胞从原条迁移所必需的。
Fgf8 and Fgf4 encode FGF family members that are coexpressed in the primitive streak of the gastrulating mouse embryo. We have analyzed the phenotype of Egf8(-/-) embryos and discovered that they fail to express Fgf4 in the streak. In the absence of both FGF8 and FGF4, epiblast cells move into the streak and undergo an epithelial-to-mesenchymal transition, but most cells then fail to move away from the streak. As a consequence, no embryonic mesoderm- or endoderm-derived tissues develop, although extraembryonic tissues form. Patterning of the prospective neuroectoderm is greatly perturbed in the mutant embryos. Anterior neuroectoderm markers are widely expressed, at least in part because the anterior visceral endoderm, which provides signals that regulate their expression, is not displaced proximally in the absence of definitive endoderm. Posterior neuroectoderm markers are not expressed, presumably because there is neither mesendoderm underlying the prospective neuroectoderm nor a morphologically normal node to provide the inductive signals necessary for their expression. This study identifies Fgf8 as a gene essential for gastrulation and shows that signaling via FGF8 and/or FGF4 is required for cell migration away from the primitive streak.