Three models of how flow breaks symmetry at the node. The node is represented in section, with the axes rotated by 90° from Figure 1; the axes are marked. (a) The morphogen hypothesis posits that a morphogen produced within the node becomes asymmetrically localized between left and right in response to flow (represented by the gray gradient). The resulting stronger left-sided signal is detected, thereby breaking symmetry. (b) The nodal vesicular parcel (NVP) hypothesis contends that morphogen-containing vesicles are carried leftwards by nodal flow, breaking in contact with cilia on the left side of the node. This delivers the morphogens within the NVPs asymmetrically, resulting in enriched morphogen signaling on the left-hand side of the node, thereby breaking symmetry. (c) The two-cilia hypothesis argues that flow itself is detected on the left side of the node by cilia-localized polycystic kidney disease (polycystin or PKD) family molecules, releasing a left-sided Ca2+ signal, thereby breaking symmetry. Single cilia of crown cells on the left and right sides of the node are represented, the one on the left becoming deformed in response to nodal flow.