The secreted factor Nodal, known as a major left determinant, is associated with severe heart defects. Yet, it has been unclear how it regulates asymmetric morphogenesis such as heart looping, which align cardiac chambers to establish the double blood circulation. Here, we report that Nodal is transiently active in precursors of the mouse heart tube poles, before looping. In conditional mutants, we show that Nodal is not required to initiate asymmetric morphogenesis. We provide evidence of a heart-specific random generator of asymmetry that is independent of Nodal. Using 3D quantifications and simulations, we demonstrate that Nodal functions as a bias of this mechanism: it is required to amplify and coordinate opposed left-right asymmetries at the heart tube poles, thus generating a robust helical shape. We identify downstream effectors of Nodal signaling, regulating asymmetries in cell proliferation, differentiation, and extracellular matrix composition. Our study uncovers how Nodal regulates asymmetric organogenesis.

分泌因子Nodal被称为主要的左决定因素，与严重的心脏缺陷有关。然而，目前尚不清楚它如何调节不对称形态，例如心脏循环，使心脏腔对齐以建立双重血液循环。在这里，我们报道在循环之前，Nodal在小鼠心管极的前体中具有瞬时活性。在条件突变体中，我们表明不需要Nodal启动不对称形态发生。我们提供了独立于Nodal的心脏特异性不对称随机发生器的证据。使用3D量化和模拟，我们证明了Nodal的作用是该机制的偏差：需要放大并协调心管两极相对的左右对称性，从而生成坚固的螺旋形状。我们确定节点信号的下游效应子，调节细胞增殖，分化和细胞外基质组成的不对称性。我们的研究揭示了Nodal如何调节不对称器官发生。