How does flt-1 affect morphogenesis?
Since flt-1-/- endothelial cells have a higher rate of division than do wild-type endothelial cells,23 it was possible that the cell division defect was immediately upstream of the morphogenetic defect. That is to say, the endothelial cells possibly were too busy dividing to migrate. There is precedent for this model in that both normal and tumor vessels restrict cell divisions to sprout areas more proximal to the parent vessel,6,7,34 suggesting that actively migrating and sensing cells are prevented from dividing. Moreover, in tubulogenesis in the fly trachea, the tracheal precursor cell pool divides to produce all the tracheal cells, which then migrate and form the tracheal tubes in the absence of further cell division.35 Our use of time-lapse image analysis allowed us to determine the relationship between cell division and cell migration with finer resolution than with end-point analyses, and it showed that endothelial cells in a migratory mode can also undergo cell division. The ce