Developing brain produces an angiogenesis factor

Abstract

Embryonic chicken brain was analyzed for the presence of growth factors for capillary endothelial cells. A growth factor was found whose total and specific activities began to increase around the 12th day of development and reached a plateau around the 14th-16th day. A high specific activity was observed early in embryonic development at days 3 and 4. The growth factor was partially purified from extracts of 18-day-old embryonic chicken brain by heparin-Sepharose affinity chromatography where it eluted as a single peak of activity at 1.2-1.4 M sodium chloride. In chromatography on Sephacryl S200 gels, the activity eluted at a molecular size of 16- to 18-kDa. The growth factor is mitogenic for endothelial cells but not for smooth muscle or glial cells. In vivo assays using rabbit cornea and chicken chorioallantoic membrane demonstrated the angiogenic capacity of the chromatographed growth factor. The relationship between this early factor, the subsequent invasion of blood vessels into neural tissue, and the formation of the blood-brain barrier is discussed.