Timeline for laterality development (A), node structure (B) and genetic cascade of LR patterning (C) in mouse. LR patterning can be divided into three steps: breakage of symmetry at the node, patterning of the LPM and asymmetric morphogenesis (A). The initial breakage of bilateral symmetry in the mouse occurs in the vicinity of the node (asterisk in A and B) at the headfold stage corresponding to embryonic day (E)7.5 to E7.8. The node is a transient structure composed of two epithelial layers: the dorsal node and the ventral node [27,123,124]. The ventral node can be separated into the pit region (red in B and C) and the crown region (marked by Cerl2 expression (black) in B). Pit cells carry mainly motile monocilia on their apical surface, whereas crown cells mainly carry immotile monocilia [11,118]. Motile monocilia of the node rotate in a clockwise orientation generating a leftward fluid flow over the node cavity (nodal flow; direction is marked by arrows in C). Nodal flow is sensed by cilia of the crown cells and converted into asymmetric signaling involving Nodal-Lefty1-Lefty2 regulatory loops in the LPM and induction of Pitx2 expression in the left LPM (C). Key players of this asymmetric signaling cascade are shown with Nodal expression in crown cells (purple) and the left LPM (green), Lefty-2 and Pitx2 expression in the left LPM (green) and Lefty-1 expression in the left side of the midline (yellow) [120,123,125-130]. I and II: scanning electron micrographs of wild type mouse embryos (I: 0 somite; II: 5 somites). III: wild type mouse embryo at E9.0 viewed from the left; B: cryo section of a mouse node after in situ hybridization using a Cerl2 probe photographed using DIC optics. c: crown cells; p: pit cells; R: right; L: left. Scale bars: 50 μm.