Centro Andaluz de Biología de Desarrollo (CABD), Univ. Pablo de Olavide-CSIC, 41013 Sevilla, Spain.
Development. 2009 Dec;136(24):4165-76. doi: 10.1242/dev.044263. Epub 2009 Nov 11.
Laminins are heterotrimeric molecules found in all basement membranes. In mammals, they have been involved in diverse developmental processes, from gastrulation to tissue maintenance. The Drosophila genome encodes two laminin alpha chains, one beta and one Gamma, which form two distinct laminin trimers. So far, only mutations affecting one or other trimer have been analysed. In order to study embryonic development in the complete absence of laminins, we mutated the gene encoding the sole laminin beta chain in Drosophila, LanB1, so that no trimers can be made. We show that LanB1 mutant embryos develop until the end of embryogenesis. Electron microscopy analysis of mutant embryos reveals that the basement membranes are absent and the remaining extracellular material appears disorganised and diffuse. Accordingly, abnormal accumulation of major basement membrane components, such as Collagen IV and Perlecan, is observed in mutant tissues. In addition, we show that elimination of LanB1 prevents the normal morphogenesis of most organs and tissues, including the gut, trachea, muscles and nervous system. In spite of the above structural roles for laminins, our results unravel novel functions in cell adhesion, migration and rearrangement. We propose that while an early function of laminins in gastrulation is not conserved in Drosophila and mammals, their function in basement membrane assembly and organogenesis seems to be maintained throughout evolution.
层粘连蛋白是存在于所有基底膜中的异三聚体分子。在哺乳动物中,它们参与了从原肠胚形成到组织维持的各种发育过程。果蝇基因组编码两种层粘连蛋白α链、一种β链和一种γ链,它们形成两种不同的层粘连蛋白三聚体。到目前为止,仅分析了影响一种或另一种三聚体的突变。为了在完全缺乏层粘连蛋白的情况下研究胚胎发育,我们突变了果蝇中唯一的层粘连蛋白β链基因 LanB1,使得无法形成三聚体。我们发现 LanB1 突变体胚胎发育到胚胎发生结束。对突变体胚胎的电子显微镜分析表明,基底膜缺失,剩余的细胞外物质看起来无序和弥散。因此,在突变组织中观察到主要基底膜成分(如 Collagen IV 和 Perlecan)的异常积累。此外,我们还表明,LanB1 的消除阻止了大多数器官和组织的正常形态发生,包括肠道、气管、肌肉和神经系统。尽管层粘连蛋白具有上述结构作用,但我们的结果揭示了其在细胞黏附、迁移和重排中的新功能。我们提出,虽然层粘连蛋白在原肠胚形成中的早期功能在果蝇和哺乳动物中没有保守,但它们在基底膜组装和器官发生中的功能似乎在整个进化过程中得到了维持。