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在果蝇胚胎发育过程中,血细胞迁移需要Fascin蛋白。

Fascin is required for blood cell migration during Drosophila embryogenesis.

作者信息

Zanet Jennifer, Stramer Brian, Millard Thomas, Martin Paul, Payre François, Plaza Serge

机构信息

Université de Toulouse, UPS, Centre de Biologie du Développement, Bâtiment 4R3, Toulouse, France.

出版信息

Development. 2009 Aug;136(15):2557-65. doi: 10.1242/dev.036517.

Abstract

Fascin is well characterized in vitro as an actin-bundling protein and its increased expression is correlated with the invasiveness of various cancers. However, the actual roles and regulation of Fascin in vivo remain elusive. Here we show that Fascin is required for the invasive-like migration of blood cells in Drosophila embryos. Fascin expression is highly regulated during embryonic development and, within the blood lineage, is specific to the motile subpopulation of cells, which comprises macrophage-like plasmatocytes. We show that Fascin is required for plasmatocyte migration, both as these cells undergo developmental dispersal and during an inflammatory response to epithelial wounding. Live analyses further demonstrate that Fascin localizes to, and is essential for the assembly of, dynamic actin-rich microspikes within plasmatocyte lamellae that polarize towards the direction of migration. We show that a regulatory serine of Fascin identified from in vitro studies is not required for in vivo cell motility, but is crucial for the formation of actin bundles within epithelial bristles. Together, these results offer a first glimpse into the mechanisms regulating Fascin function during normal development, which might be relevant for understanding the impact of Fascin in cancers.

摘要

Fascin在体外作为一种肌动蛋白成束蛋白已得到充分表征,其表达增加与多种癌症的侵袭性相关。然而,Fascin在体内的实际作用和调控机制仍不清楚。在这里,我们表明Fascin是果蝇胚胎中血细胞侵袭样迁移所必需的。Fascin的表达在胚胎发育过程中受到高度调控,并且在血细胞谱系中,特定于细胞的运动亚群,该亚群包括巨噬细胞样的浆细胞。我们表明,Fascin是浆细胞迁移所必需的,无论是在这些细胞进行发育性分散时,还是在对上皮损伤的炎症反应期间。实时分析进一步证明,Fascin定位于浆细胞薄片内动态富含肌动蛋白的微刺并对其组装至关重要,这些微刺向迁移方向极化。我们表明,从体外研究中鉴定出的Fascin的一个调节性丝氨酸对于体内细胞运动性不是必需的,但对于上皮刚毛内肌动蛋白束的形成至关重要。总之,这些结果初步揭示了正常发育过程中调节Fascin功能的机制,这可能与理解Fascin在癌症中的作用有关。

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