Time-dependent patterning of the mesoderm and endoderm by Nodal signals in zebrafish
Time-dependent patterning of the mesoderm and endoderm by Nodal signals in zebrafish
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DOI：
10.1186/1471-213x-7-22
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发表时间：
2007-03-28
影响因子：
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通讯作者：
Dougan, Scott T.
中科院分区：
文献类型：
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作者：
Hagos, Engda G.;Dougan, Scott T.
背景：在胃肠道过程中，形成三个细菌层，脊椎动物的计划是在胃肠道过程中产生的。 TGF-BETA超家族的淋巴结相关子类的成员在所有脊椎动物中诱导中胚层和内胚层。在斑马鱼中，需要以剂量依赖性的方式形成中胚层和内胚层的所有衍生物。这些基因在囊泡阶段动态表达，并且在不同时间可能具有不同的作用。这个问题很难解决，因为改变了与淋巴结相关基因表达的时机的条件也改变了淋巴结水平。我们利用药理方法在囊泡阶段有条件地使ALK 4、5和7受体灭活，而不会干扰早期的信号活性。这使我们能够直接检查节点何时指定剂量效应的何时指定细胞类型。回报：我们表明两种药物SB-431542和SB-505124，在中间大乳酸过渡后添加到胚胎时，完全阻止了对淋巴结信号的响应。 。通过在后期阶段阻止淋巴结受体活性，我们证明了从中部到弹药时期需要淋巴结信号传导才能顺序指定，Somites，Notochord，Blood，Kupffer的囊泡，孵化的腺体，心脏，心脏和内胚精。阻止晚期的淋巴结信号传导阻止了从胚胎边缘得出的细胞类型的规定，而不是来自更多动物区域的细胞类型。这表明细胞命运与暴露于淋巴结信号的长度之间存在联系。确认这一点，暴露于均匀的淋巴结剂量的细胞会逐渐更加边缘命运，而暴露的长度增加。最后，斜视突变体中的细胞命运规格被延迟，并在淋巴结水平升高时加速。结论：我们得出结论，当（1）淋巴结信号在中高囊泡阶段，当淋巴结相关的基因表达和运动时最活跃。响应细胞的最动态性； （2）淋巴结信号以时间依赖的方式指定沿着动物素食轴的细胞命运； （3）细胞响应其暴露于淋巴结信号的总累积剂量，这是距离源和暴露时间的距离的函数。
Background: The vertebrate body plan is generated during gastrulation with the formation of the three germ layers. Members of the Nodal-related subclass of the TGF-beta superfamily induce and pattern the mesoderm and endoderm in all vertebrates. In zebrafish, two nodal-related genes, called squint and cyclops, are required in a dosage-dependent manner for the formation of all derivatives of the mesoderm and endoderm. These genes are expressed dynamically during the blastula stages and may have different roles at different times. This question has been difficult to address because conditions that alter the timing of nodal-related gene expression also change Nodal levels. We utilized a pharmacological approach to conditionally inactivate the ALK 4, 5 and 7 receptors during the blastula stages without disturbing earlier signaling activity. This permitted us to directly examine when Nodal signals specify cell types independently of dosage effects.Results: We show that two drugs, SB- 431542 and SB- 505124, completely block the response to Nodal signals when added to embryos after the mid-blastula transition. By blocking Nodal receptor activity at later stages, we demonstrate that Nodal signaling is required from the mid-to-late blastula period to specify sequentially, the somites, notochord, blood, Kupffer's vesicle, hatching gland, heart, and endoderm. Blocking Nodal signaling at late times prevents specification of cell types derived from the embryo margin, but not those from more animal regions. This suggests a linkage between cell fate and length of exposure to Nodal signals. Confirming this, cells exposed to a uniform Nodal dose adopt progressively more marginal fates with increasing lengths of exposure. Finally, cell fate specification is delayed in squint mutants and accelerated when Nodal levels are elevated.Conclusion: We conclude that ( 1) Nodal signals are most active during the mid-to-late blastula stages, when nodal-related gene expression and the movement of responding cells are at their most dynamic; ( 2) Nodal signals specify cell fates along the animal-vegetal axis in a time-dependent manner; ( 3) cells respond to the total cumulative dose of Nodal signals to which they are exposed, as a function of distance from the source and duration of exposure.