Yamakita Yoshihiko, Matsumura Fumio, Yamashiro Shigeko
Department of Molecular Biology & Biochemistry, Rutgers University, Piscataway, New Jersey, USA.
Cell Motil Cytoskeleton. 2009 Aug;66(8):524-34. doi: 10.1002/cm.20356.
Fascin1, an actin-bundling protein, has been demonstrated to be critical for filopodia formation in cultured cells, and thus is believed to be vital in motile activities including neurite extension and cell migration. To test whether fascin1 plays such essential roles within a whole animal, we have generated and characterized fascin1-deficient mice. Unexpectedly, fascin1-deficient mice are viable and fertile with no major developmental defect. Nissl staining of serial coronal brain sections reveals that fascin1-deficient brain is grossly normal except that knockout mouse brain lacks the posterior region of the anterior commissure neuron and has larger lateral ventricle. Fascin1-deficient, dorsal root ganglion neurons are able to extend neurites in vitro as well as those from wild-type mice, although fascin1-deficient growth cones are smaller and exhibit fewer and shorter filopodia than wild-type counterparts. Likewise, fascin1-deficient, embryonic fibroblasts are able to assemble filopodia, though filopodia are fewer, shorter and short-lived. These results indicate that fascin1-mediated filopodia assembly is dispensable for mouse development. Cell Motil. Cytoskeleton 2009. (c) 2009 Wiley-Liss, Inc.
Fascin1是一种肌动蛋白成束蛋白，已被证明对培养细胞中丝状伪足的形成至关重要，因此被认为在包括神经突延伸和细胞迁移在内的运动活动中起着关键作用。为了测试Fascin1在整个动物体内是否发挥如此重要的作用，我们构建并鉴定了Fascin1基因敲除小鼠。出乎意料的是，Fascin1基因敲除小鼠能够存活并繁殖，没有明显的发育缺陷。对连续冠状脑切片进行尼氏染色显示，Fascin1基因敲除小鼠的大脑总体正常，只是基因敲除小鼠的大脑缺乏前连合神经元的后部区域，并且侧脑室更大。Fascin1基因敲除的背根神经节神经元在体外能够像野生型小鼠的神经元一样延伸神经突，尽管Fascin1基因敲除的生长锥较小，且与野生型相比，丝状伪足更少、更短。同样，Fascin1基因敲除的胚胎成纤维细胞能够形成丝状伪足，尽管丝状伪足数量更少、更短且寿命更短。这些结果表明，Fascin1介导的丝状伪足组装对于小鼠发育并非必不可少。《细胞运动与细胞骨架》2009年。（c）2009年威利 - 利斯公司。
