Integrin alpha 6 expression is required for early nervous system development in Xenopus laevis.
Integrin alpha 6 expression is required for early nervous system development in Xenopus laevis.
复制标题
DOI：
--
复制
发表时间：
1996-08
期刊：
影响因子：
4.6
通讯作者：
T. Lallier;C. A. Whittaker;D. DeSimone
中科院分区：
文献类型：
--
作者：
T. Lallier;C. A. Whittaker;D. DeSimone
整合素α6亚基与β1和β4亚基配对，形成层粘连蛋白受体亚家族。在这里，我们报道了哺乳动物整合素α6亚基的非洲爪哇同源基因的克隆和初步测序。我们展示了阿尔法6mRNA和蛋白在早期发育过程中的空间和时间表达。最初，α6转录本在原肠胚末期的背侧外胚层和未来的神经板中表达。在发育后期，α-6mRNAs在各种神经衍生物中表达，包括发育中的感觉安慰剂(听觉和嗅觉)和神经管内的连合神经元。整合素α6也表达于延长的前肾管和菱形脑神经脊的一个子集，它将形成排列在几条脑神经(VII、VIII和X)上的雪旺细胞。在动物大脑半球体内表达α6反义转录本会导致阿尔法6蛋白表达减少，与层粘连蛋白的粘附性丧失，并导致正常发育中的严重缺陷。在35%的情况下，阿尔法6表达水平的降低会导致胚胎正常完成原肠发育，但在神经板形成之前停止神经发育。在另外22%的病例中，胚胎发育时存在严重的轴向缺陷，包括完全丧失头部或尾部结构。相反，通过注射全长mRNA过表达α6亚基对胚胎发育没有明显影响。共注射反义和正义质粒构建物可部分挽救反义产生的表型。这些数据表明，整合素α6亚单位对两栖动物神经系统的早期发育至关重要。
The integrin alpha 6 subunit pairs with both the beta 1 and beta 4 subunits to form a subfamily of laminin receptors. Here we report the cDNA cloning and primary sequence for the Xenopus homologue of the mammalian integrin alpha 6 subunit. We present data demonstrating the spatial and temporal expression of alpha 6 mRNA and protein during early development. Initially, alpha 6 transcripts are expressed in the dorsal ectoderm and future neural plate at the end of gastrulation. Later in development, alpha 6 mRNAs are expressed in a variety of neural derivatives, including the developing sensory placodes (otic and olfactory) and commissural neurons within the neural tube. Integrin alpha 6 is also expressed in the elongating pronephric duct as well as a subset of the rhombencephalic neural crest, which will form the Schwann cells lining several cranial nerves (VII, VIII and X). In vivo expression of an alpha 6 antisense transcript in the animal hemisphere leads to a reduction in alpha 6 protein expression, a loss of adhesion to laminin, and severe defects in normal development. In 35% of cases, reduced levels of alpha 6 expression result in embryos that complete gastrulation normally but arrest at neurulation prior to the formation of the neural plate. In an additional 22% of cases, embryos develop with severe axial defects, including complete loss of head or tail structures. In contrast, overexpression of the alpha 6 subunit by injection of full-length mRNA has no apparent effect on embryonic development. Co-injection of antisense and sense plasmid constructs results in a partial rescue of the antisense-generated phenotypes. These data indicate that the integrin alpha 6 subunit is critical for the early development of the nervous system in amphibians.