Abnormalities in neural crest cell migration in laminin α5 mutant mice

Abnormalities in neural crest cell migration in laminin α5 mutant mice
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DOI:
10.1016/j.ydbio.2005.10.031
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发表时间:
2006-01-01
影响因子:
2.7
通讯作者:
Bronner-Fraser, M
Bronner-Fraser, M
中科院分区:
生物学3区
文献类型:
--
作者:
Coles, EG;Gammill, LS;Bronner-Fraser, M

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虽然大量的体外实验表明,像层粘连蛋白这样的细胞外基质分子可以影响神经脊的迁移,但对它们在胚胎中的功能知之甚少。在这里,我们证明了层粘连蛋白α5,一个在神经脊诱导过程中上调的基因,以一种在鸡和小鼠之间很大程度上保守的方式定位于新形成的颅神经和躯干神经皱折以及相邻的神经脊迁移路径的区域。在层粘连蛋白α5突变小鼠中,与野生型相比,神经峰迁移流的宽度似乎扩大了。相反,在体外暴露于层粘连蛋白α5的神经皱折显示迁移的神经脊细胞的数量减少了一半。在神经节形成过程中,层粘连蛋白α5突变体表现出凝聚颅感觉神经节和躯干交感神经节的缺陷。然而,神经节明显在后期恢复。这些数据表明,层粘连蛋白α5亚单位作为一种信号,限制神经脊细胞,集中它们的迁移路径并凝聚成神经节。因此,它对于某些神经脊种群的适当迁移和及时分化是必要的。(C)2005 Elsevier Inc.保留所有权利。
Although numerous in vitro experiments suggest that extracellular matrix molecules like laminin can influence neural crest migration, little is known about their function in the embryo. Here, we show that laminin alpha 5, a gene up-regulated during neural crest induction, is localized in regions of newly formed cranial and trunk neural folds and adjacent neural crest migratory pathways in a manner largely conserved between chick and mouse. In laminin alpha 5 mutant mice, neural crest migratory streams appear expanded in width compared to wild type. Conversely, neural folds exposed to laminin alpha 5 in vitro show a reduction by half in the number of migratory neural crest cells. During gangliogenesis, laminin alpha 5 mutants exhibit defects in condensing cranial sensory and trunk sympathetic ganglia. However, ganglia apparently recover at later stages. These data suggest that the laminin alpha 5 subunit functions as a cue that restricts neural crest cells, focusing their migratory pathways and condensation into ganglia. Thus, it is required for proper migration and timely differentiation of some neural crest populations. (c) 2005 Elsevier Inc. All rights reserved.