Left-right asymmetric heart jogging increases the robustness of dextral heart looping in zebrafish
Left-right asymmetric heart jogging increases the robustness of dextral heart looping in zebrafish
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DOI：
10.1016/j.ydbio.2019.11.012
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发表时间：
2020-03-15
影响因子：
2.7
通讯作者：
Burdine, Rebecca D.
中科院分区：
文献类型：
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作者：
Grimes, Daniel T.;Patterson, Victoria L.;Burdine, Rebecca D.
建立一个左右（L-R）不对称的器官需要不对称的信息。这来自各种来源，包括胚胎规模遗传级联（包括左侧Nodal级联）的不对称性，器官内在机械力和细胞水平手性，但这些来源的相对影响以及它们如何协作以驱动不对称形态发生尚不清楚。在斑马鱼心脏发育过程中，线性心管延伸到中线的左侧，这一过程被称为慢跑。然后，摇动的心脏经历右（即右）循环，以正确地定位心室相对于彼此。左侧偏侧慢跑是由左侧的Nodal在中胚层组织中的表达，而循环偏侧主要是由心脏内在的细胞水平的不对称性的肌动球蛋白细胞骨架。偏侧慢跑的目的尚不清楚。此外，在慢跑之后，心管返回到几乎中线的位置，因此不清楚慢跑是否或如何影响右心室环。在这里，我们描述了一种新的功能丧失突变体的斑马鱼Nodal同系物左撇子（spaw），似乎是一个真正的空。然后，我们评估之间的关系慢跑和循环偏侧胚胎缺乏不对称的Spaw信号。我们发现，右回路发生的概率，并不取决于不对称的Spaw信号本身，但取决于侧慢跑。因此，我们得出结论，慢跑的作用是空间定位的方式，促进强大的右循环的心管。当慢跑偏侧性异常时，右向环的稳健性降低。这建立了胚胎规模的Nodal依赖的L-R不对称性和器官内在细胞手性之间的合作，在控制不对称的心脏形态发生，并表明，短暂的偏侧性的早期心管有后果，后来的心脏形态发生事件。
Building a left-right (L-R) asymmetric organ requires asymmetric information. This comes from various sources, including asymmetries in embryo-scale genetic cascades (including the left-sided Nodal cascade), organ-intrinsic mechanical forces, and cell-level chirality, but the relative influence of these sources and how they collaborate to drive asymmetric morphogenesis is not understood. During zebrafish heart development, the linear heart tube extends to the left of the midline in a process known as jogging. The jogged heart then undergoes dextral (i.e. rightward) looping to correctly position the heart chambers relative to one another. Left lateralized jogging is governed by the left-sided expression of Nodal in mesoderm tissue, while looping laterality is mainly controlled by heart-intrinsic cell-level asymmetries in the actomyosin cytoskeleton. The purpose of lateralized jogging is not known. Moreover, after jogging, the heart tube returns to an almost midline position and so it is not clear whether or how jogging may impact the dextral loop. Here, we characterize a novel loss-of-function mutant in the zebrafish Nodal homolog southpaw (spaw) that appears to be a true null. We then assess the relationship between jogging and looping laterality in embryos lacking asymmetric Spaw signals. We found that the probability of a dextral loop occurring, does not depend on asymmetric Spaw signals per se, but does depend on the laterality of jogging. Thus, we conclude that the role of leftward jogging is to spatially position the heart tube in a manner that promotes robust dextral looping. When jogging laterality is abnormal, the robustness of dextral looping decreases. This establishes a cooperation between embryo-scale Nodal-dependent L-R asymmetries and organ-intrinsic cellular chirality in the control of asymmetric heart morphogenesis and shows that the transient laterality of the early heart tube has consequences for later heart morphogenetic events.