Controlled levels of canonical Wnt signaling are required for neural crest migration
Controlled levels of canonical Wnt signaling are required for neural crest migration
复制标题
DOI：
10.1016/j.ydbio.2016.06.022
复制
发表时间：
2016-09-01
影响因子：
2.7
通讯作者：
Borchers, Annette
中科院分区：
文献类型：
--
作者：
Maj, Ewa;Kuenneke, Lutz;Borchers, Annette
典型的Wnt信号在神经脊(NC)的发育中起主导作用，NC是一种高度迁移的细胞群体，产生大量的细胞类型。规范的Wnt信号是NC诱导和分化所必需的，然而它在NC迁移中的作用仍然很不清楚。分析作为典型Wnt活性读数的β-catenin的核定位，我们在迁移前的非洲爪哇NC细胞中检测到核β-catenin，但没有迁移，这表明典型的Wnt活性必须降低到基础水平才能使NC迁移。为了明确规范的Wnt信号在非洲爪哇NC迁移中的可能作用，在NC诱导后的不同时间点对规范的Wnt信号进行了调制。这是使用影响β-连环蛋白稳定性的化学调节剂或LEF/Tcf转录因子的诱导性糖皮质激素融合构建物来完成的。通过整体原位杂交对NC迁移的体内分析表明，规范的Wnt信号的异位激活抑制了NC的颅骨迁移。此外，NC移植实验证实，这种效应是组织自主的。此外，活细胞成像结合移植的NC细胞的生物物理数据分析证实了体内的发现，并证明了规范的Wnt信号的调制影响了NC细胞执行单细胞迁移的能力。因此，我们的数据支持这样的假设，即规范的Wnt信号需要被严格控制以使NC细胞能够迁移。(C)2016 Elsevier Inc.保留所有权利。
Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of beta-catenin as readout for canonical Wnt activity, we detect nuclear beta-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting beta-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. (C) 2016 Elsevier Inc. All rights reserved.