Figure 4

Developmental model. As gastrulation begins at around E6.5, the primitive streak forms and extends through the midline, establishing the anteroposterior body axis. During the process, mesoderm ingresses and begins to migrate to its ultimate position, where it will give rise to fibroblasts in muscle, preadipocytes, and endothelium. The progenitors of muscle fibroblasts and preadipocytes might arise earlier when mesoderm forms, starting from a pool of cells with fewer cell divisions (ranging from 6 to 8 divisions), while progenitors of brain endothelial cells could arise later from a few cells with a lengthier cell division history (ranging from 12 to 15 divisions). Once progenitors are established, those tissues may require similar numbers of further cell divisions to mature and develop into left and right compartments. The differing genetic identities and relative size of the progenitors for fibroblasts and preadipocytes are represented by differently colored spheres, and cell division history is indicated during mesoderm formation by color gradient, in which cells with fewer divisions appear more darkly colored. Numbers of cell divisions were calculated from the average genetic distance summarized in Table 1 using the mutation rate 0.010 for mouse 1 and 0.013 for mouse 2 as observed in this study. Schematic adapted from [46].