Draxin acts as a molecular rheostat of canonical Wnt signaling to control cranial neural crest EMT.
Draxin acts as a molecular rheostat of canonical Wnt signaling to control cranial neural crest EMT.
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DOI：
10.1083/jcb.201709149
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发表时间：
2018-10-01
期刊：
影响因子：
--
通讯作者：
Bronner ME
中科院分区：
文献类型：
--
作者：
Hutchins EJ;Bronner ME
Hutchins和Bronner表明，分泌分子Draxin的瞬时脉冲通过调节经典Wnt信号传导来调节颅神经嵴EMT沿着胚胎体前后轴的时序和进展。神经嵴细胞经历时空调节的上皮-间充质转化（EMT），其从头到尾地进行以从神经管退出。在这项研究中，我们表明，分泌的分子Draxin是在一个短暂的rostrocaudal波，反映了这种移民模式，神经嵴规范后开始和被下调之前分层。功能实验表明，Draxin通过短暂抑制经典Wnt信号传导来调节颅神经嵴EMT的时间。Draxin在颅神经管中的异位维持阻断了完全EMT;当细胞分层时，它们不能变成间充质和迁移。Draxin的损失导致过早分层，但也导致间充质化失败。这些结果表明，中间Wnt信号的脉冲触发EMT，并且是其完成所必需的。总之，这些数据表明，瞬时分泌的Draxin介导调节颅神经嵴EMT的起始和完成的精确定时所需的适当水平的经典Wnt信号传导。
Hutchins and Bronner show that a transient pulse of the secreted molecule Draxin regulates the timing and progression of cranial neural crest EMT along the anterior to posterior embryonic body axis by modulation of canonical Wnt signaling. Neural crest cells undergo a spatiotemporally regulated epithelial-to-mesenchymal transition (EMT) that proceeds head to tailward to exit from the neural tube. In this study, we show that the secreted molecule Draxin is expressed in a transient rostrocaudal wave that mirrors this emigration pattern, initiating after neural crest specification and being down-regulated just before delamination. Functional experiments reveal that Draxin regulates the timing of cranial neural crest EMT by transiently inhibiting canonical Wnt signaling. Ectopic maintenance of Draxin in the cranial neural tube blocks full EMT; while cells delaminate, they fail to become mesenchymal and migratory. Loss of Draxin results in premature delamination but also in failure to mesenchymalize. These results suggest that a pulse of intermediate Wnt signaling triggers EMT and is necessary for its completion. Taken together, these data show that transient secreted Draxin mediates proper levels of canonical Wnt signaling required to regulate the precise timing of initiation and completion of cranial neural crest EMT.
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