Baker Kari, Holtzman Nathalia G, Burdine Rebecca D
Department of Molecular Biology, Princeton University, Washington Road MOF433, Princeton, NJ 08550, USA.
Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13924-9. doi: 10.1073/pnas.0802159105. Epub 2008 Sep 10.
The Nodal signaling pathway plays a conserved role in determining left-sided identity in vertebrates with this early left-right (L/R) patterning influencing the asymmetric development and placement of visceral organs. We have studied the role of Nodal signaling in asymmetric cardiac morphogenesis in zebrafish and describe two distinct rotations occurring within the heart. The first is driven by an asymmetric migration of myocardial cells during cardiac jogging, resulting in the conversion of the L/R axis to the dorsal-ventral (D/V) axis of the linear heart. This first rotation is directly influenced by the laterality of asymmetric gene expression. The second rotation occurs before cardiac looping and positions the original left cells exposed to Nodal signaling back to the left of the wild-type (WT) heart by 48 hours postfertilization (hpf). The direction of this second rotation is determined by the laterality of cardiac jogging and is not directly influenced by asymmetric gene expression. Finally, we have identified a role for Nodal signaling in biasing the location of the inner ventricular and outer atrial curvature formations. These results suggest that Nodal signaling directs asymmetric cardiac morphogenesis through establishing and subsequently reinforcing laterality information over the course of cardiac development.
Nodal信号通路在脊椎动物确定左侧身份方面发挥着保守作用，这种早期的左右（L/R）模式影响着内脏器官的不对称发育和定位。我们研究了Nodal信号在斑马鱼心脏不对称形态发生中的作用，并描述了心脏内发生的两种不同旋转。第一种旋转是由心脏慢跑期间心肌细胞的不对称迁移驱动的，导致线性心脏的L/R轴转换为背腹（D/V）轴。第一次旋转直接受不对称基因表达的左右性影响。第二次旋转发生在心脏环化之前，并在受精后48小时（hpf）将暴露于Nodal信号的原始左侧细胞重新定位到野生型（WT）心脏的左侧。第二次旋转的方向由心脏慢跑的左右性决定，不受不对称基因表达的直接影响。最后，我们确定了Nodal信号在偏向于心室内外曲率形成位置方面的作用。这些结果表明，Nodal信号通过在心脏发育过程中建立并随后加强左右性信息来指导心脏不对称形态发生。
