Embryonic vascular system undergoes a series of complex, highly regulated series of events involving differentiation, migration and association of primitive endothelial cells. This process is termed vasculogenesis. A further remodeling of the primitive vascular system forms the mature cardiovascular system. This process is known as angiogenesis (sprouting of new capillary vessels from pre-existing vasculature). Angiogenesis accounts for the formation of vasculature into previously avascular organs such as brain and kidney. Angiogenic activity in the adult is required during normal tissue repair, and for the remodeling of the female reproductive organs (ovulation and placental development). Certain pathological conditions, such as tumor growth and diabetic retinopathy, also require angiogenesis. Study of tumor angiogenesis has led to the identification of several proteins in the angiogenic pathway. Angiopoietin-1 is an angiogenic secreted protein that interacts with endothelial specific Tie-2 receptor. It is primarily expressed in developing endothelial cells. During embryonic development, Ang-1 binds and induces tyrosine phosphorylation of Tie-2. Ang-1 may play a critical role in heart development. A homolog of Ang-1, termed Angiopoietin-2 (mouse and human Ang-2, 496aa; ~85% identity) has recently been identified. It may act as an antagonist for Ang-1 and Tie-2. Ang-1 and Ang-2 have ~60% sequence homology.