Sox2 and Canonical Wnt Signaling Interact to Activate a Developmental Checkpoint Coordinating Morphogenesis with Mesoderm Fate Acquisition.
Sox2 and Canonical Wnt Signaling Interact to Activate a Developmental Checkpoint Coordinating Morphogenesis with Mesoderm Fate Acquisition.
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DOI：
10.1016/j.celrep.2020.108311
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发表时间：
2020-10-27
期刊：
影响因子：
8.8
通讯作者：
Martin BL
中科院分区：
文献类型：
--
作者：
Kinney BA;Al Anber A;Row RH;Tseng YJ;Weidmann MD;Knaut H;Martin BL
动物胚胎发生需要形态发生和细胞命运规范之间的精确协调。在中胚层诱导过程中，中胚层命运获得与上皮-间充质转化（EMT）的形态发生过程密切协调。在斑马鱼中，细胞在中胚层诱导过程中短暂地处于部分EMT状态。在这里，我们发现表达转录因子Sox2的细胞被保持在部分EMT状态，阻止它们完成EMT并加入中胚层。这对于防止异位神经组织的形成至关重要。其机制涉及Sox2与中胚层诱导的典型Wnt信号通路之间的协同作用。当Wnt信号在部分EMT中表达sox2的细胞中被抑制时，细胞进入中胚层领域，但形成异位脊髓而不是中胚层。我们的工作确定了一个关键的发育检查点，确保建立中胚层的形态发生运动伴随着稳健的中胚层细胞命运获得。在胚胎发育过程中，正确的组织类型必须在适当的位置形成。Kinney等人表明，发育检查点在中胚层诱导过程中起作用，确保表达sox2的细胞不会迁移到中胚层。这个检查点对于防止异位脊髓取代中胚层形成至关重要。
Animal embryogenesis requires a precise coordination between morphogenesis and cell fate specification. During mesoderm induction, mesodermal fate acquisition is tightly coordinated with the morphogenetic process of epithelial-to-mesenchymal transition (EMT). In zebrafish, cells exist transiently in a partial EMT state during mesoderm induction. Here, we show that cells expressing the transcription factor Sox2 are held in the partial EMT state, stopping them from completing the EMT and joining the mesoderm. This is critical for preventing the formation of ectopic neural tissue. The mechanism involves synergy between Sox2 and the mesoderm-inducing canonical Wnt signaling pathway. When Wnt signaling is inhibited in Sox2-expressing cells trapped in the partial EMT, cells exit into the mesodermal territory but form an ectopic spinal cord instead of mesoderm. Our work identifies a critical developmental checkpoint that ensures that morphogenetic movements establishing the mesodermal germ layer are accompanied by robust mesodermal cell fate acquisition. During embryonic development, the right tissue types must form in the proper location. Kinney et al. show that a developmental checkpoint functions during mesoderm induction, ensuring that Sox2-expressing cells do not migrate into the mesoderm. This checkpoint is critical for preventing ectopic spinal cord from forming in place of mesoderm.
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