How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration.
How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration.
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DOI：
10.1038/srep20927
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发表时间：
2016-02-18
影响因子：
4.6
通讯作者：
Fleury V
中科院分区：
文献类型：
--
作者：
Chevalier NR;Gazguez E;Bidault L;Guilbert T;Vias C;Vian E;Watanabe Y;Muller L;Germain S;Bondurand N;Dufour S;Fleury V
神经嵴细胞（NCCs）是一群多能细胞，在脊椎动物发育过程中广泛迁移。神经嵴个体发育的改变导致几种疾病，包括癌症和先天性缺陷，例如Hirschprung病，其由肠道NCC（ENCC）对结肠的不完全定殖引起。我们调查的刚度和结构的环境对ENCC迁移在体外和在鸡和小鼠胚胎的胃肠道定植的影响。我们表明，使用拉伸拉伸和原子力显微镜（AFM）的肠道间充质最初是软的，但逐渐变硬期间ENCC殖民。二次谐波发生（SHG）显微镜显示，这种硬化与逐渐组织和丰富的胶原纤维在发展中的肠道。离体2D细胞迁移测定显示，ENCC在具有非常低水平的刚度的基底上迁移。在3D胶原凝胶中，ENCC迁移前沿的速度随着凝胶刚度的增加而降低，而孔隙率和ENCC迁移行为之间没有相关性。金属蛋白酶抑制实验表明，ENCCs积极降解胶原蛋白，以进步。这些结果揭示了组织的机械性能在ENCC迁移过程中的作用。
Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.