Formation of the branching pattern of blood vessels in the wall of the avian yolk sac studied by a computer simulation.

The present study was performed to provide data to support the notion previously believed but not proved experimentally or theoretically, that blood vessels are formed by the selection of capillaries in the network. In an attempt to understand the mechanism of formation of blood vessel branching structures, the transformation of a capillary network to a branching system in the wall of quail yolk sac was successively recorded by a series of photographs, and a computer simulation was carried out for the process of in vivo vascularization based on the photographs. The simulation demonstrated that a positive feedback system participated in the formation of a branching structure. That is, vessels which had been much used were enlarged, whereas less used vessels were reduced in their size and finally extinguished. The enlarged vessels became major components of the branching system. As the body of an embryo grew, it was observed that polygonal capillary networks enlarged, which led each polygon of the network to divide into a few finer polygons. Then, some of the capillary vessels were again selected and formed a branching system. This process repeated during the body growth, indicating that the vascular system developed adaptively to the body growth. A region where the growth was fast, received much blood flow and produced finer networks of capillaries. Thus, it was experimentally demonstrated for the first time that capillaries in the network are successively selected by a positive feedback mechanism and form blood vessels.