Angiopoietin 2 signaling plays a critical role in neural crest cell migration.

Angiopoietin 2 signaling plays a critical role in neural crest cell migration.
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DOI:
10.1186/s12915-016-0323-9
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发表时间:
2016-12-15
期刊:
影响因子:
5.4
通讯作者:
Kulesa PM
Kulesa PM
中科院分区:
生物学2区
文献类型:
--
作者:
McKinney MC;McLennan R;Kulesa PM

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集体神经嵴细胞迁移对于脊椎动物面部和颈部的形态和功能至关重要,它将骨、软骨和神经细胞分布到与头部脉管系统密切相关的外周目标中。脉管系统和神经嵴结构最终是相关的,但这些模式在早期胚胎中何时以及如何发育尚不清楚。利用体内成像和复杂的细胞行为分析,我们表明鹌鹑颅神经嵴和内皮细胞具有共同的迁移路径,在动态多步骤过程中进行分类,并显示多种类型的运动。为了更好地了解潜在的分子信号,我们检查了血管生成素 2 (Ang2) 的作用,我们发现它在迁移的颅神经嵴细胞中表达。 Ang2 的过度表达导致神经嵴细胞更具探索性,如侵入脱靶位置、扩大迁移流至禁止区域以及细胞运动类型的差异。探索性表型的增强与迁移神经嵴细胞中磷酸化粘着斑激酶活性的增加相关。相反,Ang2 功能的丧失会减少神经嵴细胞的探索。在 Ang2 功能的获得和丧失中,我们发现颅神经嵴和内皮细胞之间的时间安排和相互作用受到破坏。总之,这些数据证明了 Ang2 在维持集体颅神经嵴细胞迁移中的作用,并表明在脊椎动物头部模式形成过程中与内皮细胞迁移的相互依赖性。本文的在线版本 (doi:10.1186/s12915-016-0323-9) 包含补充材料,可供授权用户使用。
Collective neural crest cell migration is critical to the form and function of the vertebrate face and neck, distributing bone, cartilage, and nerve cells into peripheral targets that are intimately linked with head vasculature. The vasculature and neural crest structures are ultimately linked, but when and how these patterns develop in the early embryo are not well understood. Using in vivo imaging and sophisticated cell behavior analyses, we show that quail cranial neural crest and endothelial cells share common migratory paths, sort out in a dynamic multistep process, and display multiple types of motion. To better understand the underlying molecular signals, we examined the role of angiopoietin 2 (Ang2), which we found expressed in migrating cranial neural crest cells. Overexpression of Ang2 causes neural crest cells to be more exploratory as displayed by invasion of off-target locations, the widening of migratory streams into prohibitive zones, and differences in cell motility type. The enhanced exploratory phenotype correlates with increased phosphorylated focal adhesion kinase activity in migrating neural crest cells. In contrast, loss of Ang2 function reduces neural crest cell exploration. In both gain and loss of function of Ang2, we found disruptions to the timing and interplay between cranial neural crest and endothelial cells. Together, these data demonstrate a role for Ang2 in maintaining collective cranial neural crest cell migration and suggest interdependence with endothelial cell migration during vertebrate head patterning. The online version of this article (doi:10.1186/s12915-016-0323-9) contains supplementary material, which is available to authorized users.
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