Melloy P G, Ewart J L, Cohen M F, Desmond M E, Kuehn M R, Lo C W
Department of Biology, University of Pennsylvania, Philadelphia 19104, USA.
Dev Biol. 1998 Jan 1;193(1):77-89. doi: 10.1006/dbio.1997.8787.
Patterning along the left/right axes helps establish the orientation of visceral organ asymmetries, a process which is of fundamental importance to the viability of an organism. A linkage between left/right and axial patterning is indicated by the finding that a number of genes involved in left/right patterning also play a role in anteroposterior and dorsoventral patterning. We have recovered a spontaneous mouse mutation causing left/right patterning defects together with defects in anteroposterior and dorsoventral patterning. This mutation is recessive lethal and was named no turning (nt) because the mutant embryos fail to undergo embryonic turning. nt embryos exhibit cranial neural tube closure defects and malformed somites and are caudally truncated. Development of the heart arrests at the looped heart tube stage, with cardiovascular defects indicated by ballooning of the pericardial sac and the pooling of blood in various regions of the embryo. Interestingly, in nt embryos, the direction of heart looping was randomized. Nodal and lefty, two genes that are normally expressed only in the left lateral plate mesoderm, show expression in the right and left lateral plate mesoderm. Lefty, which is normally also expressed in the floorplate, is not found in the prospective floor plate of nt embryos. This suggests the possibility of notochordal defects. This was confirmed by histological analysis and the examination of sonic hedgehog, Brachyury, and HNF-3 beta gene expression. These studies showed that the notochord is present in the early nt embryo, but degenerates as development progresses. Overall, these findings support the hypothesis that the notochord plays an active role in left/right patterning. Our results suggest that nt may participate in this process by modulating the notochordal expression of HNF-3 beta.
沿左右轴的模式形成有助于确立内脏器官不对称性的方向，这一过程对生物体的生存能力至关重要。参与左右模式形成的一些基因也在前后和背腹模式形成中发挥作用，这一发现表明左右模式形成与轴模式形成之间存在联系。我们发现了一种自发的小鼠突变，它导致左右模式形成缺陷以及前后和背腹模式形成缺陷。这种突变是隐性致死的，被命名为无旋转（nt），因为突变胚胎无法进行胚胎旋转。nt胚胎表现出颅神经管闭合缺陷和体节畸形，并且尾部截断。心脏发育在心脏管成环阶段停止，心包囊膨胀以及胚胎各区域血液积聚表明存在心血管缺陷。有趣的是，在nt胚胎中，心脏成环方向是随机的。Nodal和Lefty这两个通常仅在左侧板中胚层表达的基因，在右侧和左侧板中胚层均有表达。通常也在地板表达的Lefty，在nt胚胎的预期地板中未被发现。这提示了脊索缺陷的可能性。组织学分析以及对音猬因子、短尾相关蛋白和肝细胞核因子3β基因表达的检测证实了这一点。这些研究表明，脊索在早期nt胚胎中存在，但随着发育进程会退化。总体而言，这些发现支持了脊索在左右模式形成中发挥积极作用的假说。我们的结果表明，nt可能通过调节肝细胞核因子3β的脊索表达来参与这一过程。
