Randall Centre for Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
Randall Centre for Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
Curr Biol. 2017 Nov 20;27(22):3526-3534.e4. doi: 10.1016/j.cub.2017.10.001. Epub 2017 Nov 9.
The basement membrane (BM) is a thin layer of extracellular matrix (ECM) beneath nearly all epithelial cell types that is critical for cellular and tissue function. It is composed of numerous components conserved among all bilaterians [1]; however, it is unknown how all of these components are generated and subsequently constructed to form a fully mature BM in the living animal. Although BM formation is thought to simply involve a process of self-assembly [2], this concept suffers from a number of logistical issues when considering its construction in vivo. First, incorporation of BM components appears to be hierarchical [3-5], yet it is unclear whether their production during embryogenesis must also be regulated in a temporal fashion. Second, many BM proteins are produced not only by the cells residing on the BM but also by surrounding cell types [6-9], and it is unclear how large, possibly insoluble protein complexes [10] are delivered into the matrix. Here we exploit our ability to live image and genetically dissect de novo BM formation during Drosophila development. This reveals that there is a temporal hierarchy of BM protein production that is essential for proper component incorporation. Furthermore, we show that BM components require secretion by migrating macrophages (hemocytes) during their developmental dispersal, which is critical for embryogenesis. Indeed, hemocyte migration is essential to deliver a subset of ECM components evenly throughout the embryo. This reveals that de novo BM construction requires a combination of both production and distribution logistics allowing for the timely delivery of core components.
基底膜（BM）是几乎所有上皮细胞类型下方的一层薄细胞外基质（ECM），对于细胞和组织功能至关重要。它由所有两侧对称动物中保守的许多成分组成[1]；然而，尚不清楚所有这些成分是如何产生的，以及随后如何构建以在活体动物中形成完全成熟的 BM。尽管 BM 的形成被认为只是涉及一个自我组装的过程[2]，但当考虑其在体内构建时，这个概念存在许多逻辑问题。首先，BM 成分的掺入似乎是分层的[3-5]，但尚不清楚它们在胚胎发生期间的产生是否也必须以时间方式进行调节。其次，许多 BM 蛋白不仅由位于 BM 上的细胞产生，而且还由周围的细胞类型产生[6-9]，尚不清楚如何将大型、可能不溶性的蛋白复合物[10]递送到基质中。在这里，我们利用我们在果蝇发育过程中实时成像和遗传剖析新形成的 BM 的能力。这表明存在 BM 蛋白产生的时间层次结构，对于正确的成分掺入至关重要。此外，我们表明 BM 成分在其发育分散过程中需要迁移巨噬细胞（血细胞）分泌，这对于胚胎发生至关重要。事实上，血细胞迁移对于将一组 ECM 成分均匀地递送到胚胎中至关重要。这表明新形成的 BM 构建需要生产和分配物流的组合，以允许核心成分的及时递送。
