Schmid Ralf S, Shelton Stephanie, Stanco Amelia, Yokota Yukako, Kreidberg Jordan A, Anton E S
UNC Neuroscience Center and the Department of Cell and Molecular Physiology, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Development. 2004 Dec;131(24):6023-31. doi: 10.1242/dev.01532. Epub 2004 Nov 10.
We show that alpha3 integrin mutation disrupts distinct aspects of neuronal migration and placement in the cerebral cortex. The preplate develops normally in alpha3 integrin mutant mice. However, time lapse imaging of migrating neurons in embryonic cortical slices indicates retarded radial and tangential migration of neurons, but not ventricular zone-directed migration. Examination of the actin cytoskeleton of alpha3 integrin mutant cortical cells reveals aberrant actin cytoskeletal dynamics at the leading edges. Deficits are also evident in the ability of developing neurons to probe their cellular environment with filopodial and lamellipodial activity. Calbindin or calretinin positive upper layer neurons as well as the deep layer neurons of alpha3 integrin mutant mice expressing EGFP were misplaced. These results suggest that alpha3beta1 integrin deficiency impairs distinct patterns of neuronal migration and placement through dysregulated actin dynamics and defective ability to search and respond to migration modulating cues in the developing cortex.
我们发现α3整合素突变会破坏神经元在大脑皮层中迁移和定位的不同方面。在α3整合素突变小鼠中，前板发育正常。然而，对胚胎皮质切片中迁移神经元的延时成像显示，神经元的径向和切向迁移受阻，但室管膜区导向的迁移不受影响。对α3整合素突变皮质细胞的肌动蛋白细胞骨架进行检查，发现前沿的肌动蛋白细胞骨架动力学异常。发育中的神经元通过丝状伪足和片状伪足活动探测细胞环境的能力也明显不足。表达EGFP的α3整合素突变小鼠中，钙结合蛋白或钙视网膜蛋白阳性的上层神经元以及深层神经元位置异常。这些结果表明，α3β1整合素缺乏会通过肌动蛋白动力学失调以及在发育中的皮层中搜索和响应迁移调节线索的能力缺陷，损害神经元迁移和定位的不同模式。
