Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts

Id proteins may control cell differentiation by interfering with DNA bindin g of transcription factors. Here we show that targeted disruption of the do minant negative helix-loop-helix proteins Id1 and ld3 in mice results in pr emature withdrawal of neuroblasts from the cell cycle and expression of neu ral-specific differentiation markers. The ld1-ld3 double knockout mice also display vascular malformations in the forebrain and an absence of branchin g and sprouting of blood vessels into the neuroectoderm. As angiogenesis bo th in the brain and in tumours requires invasion of avascular tissue by end othelial cells, we examined the Id knockout mice for their ability to suppo rt the growth of tumour xenografts, Three different tumours failed to grow and/or metastasize in ld1(+/-)ld3(-/-) mice, and any tumour growth present showed poor vascularization and extensive necrosis, Thus, the Id genes are required to maintain the timing of neuronal differentiation in the embryo a nd invasiveness of the vasculature, Because the Id genes are expressed at v ery low levels in adults, they make attractive new targets for anti-angioge nic drug design.