Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
PLoS One. 2013;8(1):e54410. doi: 10.1371/journal.pone.0054410. Epub 2013 Jan 22.
The development of specialized organs is tightly linked to the regulation of cell growth, orientation, migration and adhesion during embryogenesis. In addition, the directed movements of cells and their orientation within the plane of a tissue, termed planar cell polarity (PCP), appear to be crucial for the proper formation of the body plan. In Drosophila embryogenesis, Discs large (dlg) plays a critical role in apical-basal cell polarity, cell adhesion and cell proliferation. Craniofacial defects in mice carrying an insertional mutation in Dlgh-1 suggest that Dlgh-1 is required for vertebrate development. To determine what roles Dlgh-1 plays in vertebrate development, we generated mice carrying a null mutation in Dlgh-1. We found that deletion of Dlgh-1 caused open eyelids, open neural tube, and misorientation of cochlear hair cell stereociliary bundles, indicative of defects in planar cell polarity (PCP). Deletion of Dlgh-1 also caused skeletal defects throughout the embryo. These findings identify novel roles for Dlgh-1 in vertebrates that differ from its well-characterized roles in invertebrates and suggest that the Dlgh-1 null mouse may be a useful animal model to study certain human congenital birth defects.
专门器官的发育与胚胎发生过程中细胞生长、定向、迁移和黏附的调节密切相关。此外，细胞的定向运动及其在组织平面内的取向，即平面细胞极性（PCP），对于身体计划的正确形成似乎至关重要。在果蝇胚胎发生过程中，Discs large（dlg）在顶端-基底细胞极性、细胞黏附和细胞增殖中发挥着关键作用。携带 Dlgh-1 插入突变的小鼠出现颅面缺陷，表明 Dlgh-1 是脊椎动物发育所必需的。为了确定 Dlgh-1 在脊椎动物发育中的作用，我们生成了 Dlgh-1 缺失突变的小鼠。我们发现 Dlgh-1 的缺失导致眼皮张开、神经管张开以及耳蜗毛细胞静纤毛束的错位，表明 PCP 存在缺陷。Dlgh-1 的缺失还导致胚胎中出现骨骼缺陷。这些发现确定了 Dlgh-1 在脊椎动物中的新作用，与它在无脊椎动物中的特征作用不同，并表明 Dlgh-1 缺失小鼠可能是研究某些人类先天性出生缺陷的有用动物模型。
