Fig 6. Stalk cell division.

Panel A depicts initial sprouting with both stalk (S) cells fully matured, while Panel B shows the initial placement of the daughter cells. Panel C depicts how the combination of continued stalk cell proliferation and migration of the tip cell due to the VEGF gradient leads to elongation of the sprout. The stalk cell phenotype is governed by complex signaling pathways and local variations in the VEGF field [52]. Since these pathways (primarily the notch signaling pathway) are contact dependent, the stalk cell phenotype is fundamentally limited by its distance to a tip cell. We simplify this process by implementing a distance threshold d_SE, the distance from a tip cell where a stalk cell will transition to a phalanx cell. Finally, Panel D displays that the growing stalk and phalanx cells are fully matured, and the process restarts again from Panel A. This process is continued repeatedly to allow sprout elongation in the direction of the gradient of VEGF.