Asymmetric distribution of hypoxia-inducible factor α regulates dorsoventral axis establishment in the early sea urchin embryo
Asymmetric distribution of hypoxia-inducible factor α regulates dorsoventral axis establishment in the early sea urchin embryo
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DOI：
10.1242/dev.145052
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发表时间：
2017-08-15
期刊：
影响因子：
4.6
通讯作者：
Su, Yi-Hsien
中科院分区：
文献类型：
--
作者：
Chang, Wei-Lun;Chang, Yi-Cheng;Su, Yi-Hsien
低氧信号是动物对低氧做出反应的一条古老的途径。这一通路的故障会扰乱低氧适应，并可能导致包括癌症在内的各种疾病。低氧信号在早期胚胎发育中的作用尚不清楚。在这里，我们发现在紫球海胆的囊胚中，低氧途径的下游转录因子低氧诱导因子α(HIFα)定位于未来的背侧，并在转录上具有活性。这种不对称分布归因于它的氧气传感能力。对HIFα水平的操纵牵涉到背腹轴，因为HIFα水平较高的一侧倾向于向背侧发展。基因表达分析表明，HIFα将结节的表达限制在腹侧，并激活了背侧的几个编码转录因子的基因。我们还观察到早期胚胎中固有的低氧信号形成了一个梯度，这种梯度在低氧条件下被破坏。我们的结果揭示了低氧途径在动物发育中的前所未有的作用。
Hypoxia signaling is an ancient pathway by which animals can respond to low oxygen. Malfunction of this pathway disturbs hypoxic acclimation and can result in various diseases, including cancers. The role of hypoxia signaling in early embryogenesis remains unclear. Here, we show that in the blastula of the sea urchin Strongylocentrotus purpuratus, hypoxia-inducible factor alpha (HIF alpha), the downstream transcription factor of the hypoxia pathway, is localized and transcriptionally active on the future dorsal side. This asymmetric distribution is attributable to its oxygen-sensing ability. Manipulations of the HIF alpha level entrained the dorsoventral axis, as the side with the higher level of HIF alpha tends to develop into the dorsal side. Gene expression analyses revealed that HIF alpha restricts the expression of nodal to the ventral side and activates several genes encoding transcription factors on the dorsal side. We also observed that intrinsic hypoxic signals in the early embryos formed a gradient, which was disrupted under hypoxic conditions. Our results reveal an unprecedented role of the hypoxia pathway in animal development.