Figure 1: A mathematical model of the corneal epithelium recapitulates centripetal migration and clonal segmentation.
From: Self-organized centripetal movement of corneal epithelium in the absence of external cues
(a) A scheme of cell lineages in the cornea simulation model. The conjunctiva (Cj) forms an impenetrable perimeter. LESCs can divide either symmetrically, to produce two LESCs, or asymmetrically, to produce a LESC that is retained within the limbus and a TAC that occupies a space in the cornea immediately adjacent to the limbus. When a LESC dies, the two neighbouring LESCs are stimulated to replicate to fill the void, only one of them being able to occupy the space. TACs can divide either asymmetrically, to produce a suprabasal terminally differentiating cell (TDC) and another TAC in the basal layer, or symmetrically, to produce two TACs in the basal layer. TACs can undergo a limited number of symmetrical cell divisions, TAC(max), which is variable but typically set at 3, after which they die. The number of symmetric replications remaining for a TAC is shown in parentheses. (b) A representative simulation in which the replicative potential of TACs is limited to 4 symmetrical cell divisions and development has been allowed to continue for 750 iterations of the algorithm. The numbered spokes provide direction reference points (in radians) for the location of clones in e. (c) A fluorescence micrograph of a cornea from a K14CreERT2-Confetti mouse, injected with tamoxifen when 6 weeks old and killed 16 weeks later. The circular haze in the centre of the cornea is autofluorescence from the underlying lens. Scale bar, 500 μm. (d) The number of clonal lineages of all cells (blue) and only LESCs (black), plotted ±s.d. against time for 25 simulations. (e) The spread of cells of a lineage was plotted for 10 representative clones of the cornea shown in b. The distance is measured as a proportion of the corneal radius. The locations and mean linear displacements (LDs) of these clones are reported in Supplementary Table 1. (f) Calculation of the LD, a measure of the degree to which migration is centripetal. The locations of a TAC in a cornea and the LESC from which it is derived are shown. If migration of the LESC-derived lineage was perfectly centripetal, then the TAC would lie on the ray joining the position of the LESC to the centre of the cornea (the LESCR). The LD is the absolute distance of the perpendicular from the TAC to this ray.
