FGF8 acts as a right determinant during establishment of the left-right axis in the rabbit
FGF8 acts as a right determinant during establishment of the left-right axis in the rabbit
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DOI：
10.1016/s0960-9822(02)01222-8
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发表时间：
2002-10-29
期刊：
影响因子：
9.2
通讯作者：
Blum, M
中科院分区：
文献类型：
--
作者：
Fischer, A;Viebahn, C;Blum, M
背景资料：FGF 8参与左右（L-R）不对称性从胚胎中线（结节）转移到侧板中胚层（LPM）。令人惊讶的是，在鸡和小鼠中描述了相反的作用。在小鼠中，FGF 8是nodal、lefty 2和Pitx 2的左不对称表达所必需的。在鸡中，FGF 8在右侧抑制nodal和Pitx 2。这种差异可能反映了鸟类和哺乳动物之间的进化差异。另外，fgf 8的右不对称表达，这是没有发现在小鼠，在鸡结可能是一个先决条件的右侧功能。最后，鸡（blastodisc）和小鼠（卵柱）不同的拓扑结构的早期原肠胚/神经胚embryon.Results：兔blastodisc进行了研究，作为一个额外的哺乳动物L-R模型系统。虽然nodal、lefty和Pitx 2在左侧LPM中显示不对称表达，但fgf 8和所有其他中线标记基因在小鼠中在结节样处对称表达。左侧应用FGF 8抑制内源性转录的结节以及异位表达诱导的并行管理的BMP 4。右侧抑制FGF 8信号诱导的双边标记基因的表达，表明，在兔，FGF 8作为一个正确的决定因素，如在chick.Conclusions：这些研究结果表明，解剖的早期胚胎（blastodisc与卵缸），而不是分类差异或不对称的表达构成了一个重要的决定因素，在L-R轴形成的FGF 8功能。兔子可能为早期人类胚胎发育提供有用的模型，因为人类胚胎也是通过胚盘发育的。
Background: FGF8 has been implicated in the transfer of left-right (L-R) asymmetry from the embryonic midline (node) to the lateral plate mesoderm (LPM). Surprisingly, opposite roles have been described in chick and mouse. In mouse, FGF8 is required for the left-asymmetric expression of nodal, lefty2, and Pitx2. In chick, FGF8 represses nodal and Pitx2 on the right side. This discrepancy could reflect evolutionary differences between birds and mammals. Alternatively, the right-asymmetric expression of fgf8, which is not found in mouse, at the chick node may be a prerequisite of right-sided function. Finally, chick (blastodisc) and mouse (egg cylinder) differ with respect to the topology of the early gastrula/neurula embryo.Results: The rabbit blastodisc was investigated as an additional mammalian L-R model system. While nodal, lefty, and Pitx2 showed asymmetric expression in the left LPM, fgf8 and all other midline marker genes were symmetrically expressed at the node like in mouse. Left-sided application of FGF8 repressed the endogenous transcription of nodal as well as ectopic expression induced by the parallel administration of BMP4. Right-sided inhibition of FGF8 signaling induced bilateral marker gene expression, demonstrating that, in rabbit, FGF8 acts as a right determinant like in chick.Conclusions: These findings suggest that the anatomy of the early embryo (blastodisc versus egg cylinder) rather than taxonomical differences or asymmetry in expression constitutes an important determinant of FGF8 function in L-R axis formation. The rabbit may provide a useful model for early human embryogenesis, as human embryos develop via a blastodisc as well.