Xenopus nodal-related signaling is essential for mesendodermal patterning during early embryogenesis.
Xenopus nodal-related signaling is essential for mesendodermal patterning during early embryogenesis.
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发表时间：
1999-07
期刊：
影响因子：
4.6
通讯作者：
S. Osada;C. V. Wright
中科院分区：
文献类型：
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作者：
S. Osada;C. V. Wright
以前，我们表明，非洲爪蟾胚胎相关因子（Xnrs）可以作为中胚层诱导剂，激活素诱导Xnr转录，这表明Xnrs中继或维持激活素样分子启动的诱导过程。我们使用一个显性负切割突变体Xnr 2（cmXnr 2）进行功能丧失实验，以探讨在早期两栖动物胚胎发生的Xnr信号的需求，以及激活素和Xnrs之间的关系。cmXnr 2阻断了由Xnr而不是激活素RNA引起的中胚层诱导。相比之下，cmXnr 2确实抑制激活素蛋白的中胚层和内胚层诱导，而Xnr转录物诱导不受cmXnr 2的影响，这与激活素蛋白处理诱导的Xnr肽的功能的干扰一致。严重hyperdorsalization和原肠胚缺陷造成的Xnr 2在整个胚胎中被拯救cmXnr 2，建立一个特定的拮抗关系之间的正常和切割突变蛋白。cmXnr 2的表达导致延迟的背唇形成和一系列的前截断与延迟和抑制的背前内胚层，其中最近公认的头部组织者活动的标志物的表达。反过来，Xnr 2诱导背前内胚层标记，如cerberus，Xhex-1和Frzb，在动物帽外胚层。从cmXnr 2 RNA注射胚胎中分离的头部中内胚层的迁移行为急剧减少。这些结果表明，Xnrs在启动原肠胚形成中起着至关重要的作用，可能是通过激活素样信号通路的下游作用，该通路导致背侧中内胚层特化，包括建立头部组织者。
Previously, we showed that Xenopus nodal-related factors (Xnrs) can act as mesoderm inducers, and that activin induces Xnr transcription, suggesting that Xnrs relay or maintain induction processes initiated by activin-like molecules. We used a dominant negative cleavage mutant Xnr2 (cmXnr2) to carry out loss-of-function experiments to explore the requirement for Xnr signaling in early amphibian embryogenesis, and the relationship between activin and Xnrs. cmXnr2 blocked mesoderm induction caused by Xnr, but not activin, RNA. In contrast, cmXnr2 did suppress mesoderm and endoderm induction by activin protein, while Xnr transcript induction was unaffected by cmXnr2, consistent with an interference with the function of Xnr peptides that were induced by activin protein treatment. The severe hyperdorsalization and gastrulation defects caused by Xnr2 in whole embryos were rescued by cmXnr2, establishing a specific antagonistic relationship between the normal and cleavage mutant proteins. Expression of cmXnr2 resulted in delayed dorsal lip formation and a range of anterior truncations that were associated with delayed and suppressed expression of markers for dorsoanterior endoderm, in which the recently recognized head organizer activity resides. Reciprocally, Xnr2 induced dorsoanterior endodermal markers, such as cerberus, Xhex-1 and Frzb, in animal cap ectoderm. The migratory behavior of head mesendoderm explanted from cmXnr2 RNA-injected embryos was drastically reduced. These results indicate that Xnrs play crucial roles in initiating gastrulation, probably by acting downstream of an activin-like signaling pathway that leads to dorsal mesendodermal specification, including setting up the head organizer.