Role of Id proteins in embryonic and tumor angiogenesis.

It has been shown recently in mouse model systems that the Id proteins play a critical role in angiogenesis both during embryogenesis and tumor formation. The Id proteins are intracellular proteins that inhibit the activity of differentiation-promoting transcription factors and thereby block differentiation and promote cell cycle progression. Loss of Id function in mice leads to premature neural differentiation and withdrawal from the cell cycle in neurons and also the execution of an aberrant differentiation cascade in endothelial cells. This latter event is associated with a mid-gestational brain hemorrhage when Id dosage is sufficiently low. Partial reduction in Id levels spares the endothelium in the brain but adults born fail to support the vascularization of tumors. Through the analysis of these phenotypes and characterization of altered gene expression in the Id knockout endothelium, subdivisions in the angiogenic process are being defined which may lead to selective anti-angiogenic treatments in the management of human disease.