Neuronal processes and vessels have similar branching and bifurcation patterning in the adult body and appear to use many of the same molecules during their development, including vascular endothelial growth factor, Notch, neuropilin, and ephrins/Ephs. We were interested in determining whether the endothelial growth factor angiopoietin (Ang) has a unique role in the nervous system in addition to its angiogenic role. By using a mouse molecular genetics approach, we overexpressed Ang1 in the mouse forebrain and observed increases in overall vascularization, consistent with prior reports describing the role of Ang1. Nonvascular events, involving alterations in the dendritic organization of layer II motor cortex neurons, dentate granule cells, and pyramidal cells of CA1, were seen, suggesting that Ang1 was able to influence the growth of these processes. The angiopoietin tyrosine kinase receptor Tie2 was not found on neurons or their processes, but beta1 integrin was and has previously been found to act as an Ang receptor. Our findings provide some of the first data evaluating the interactions between the developing nervous system and the vascular protein Ang1. Understanding interactions between the developing nervous and vascular systems will lead to novel insight into how the two systems interact throughout development, during senescence, and in disease.
2004 Wiley-Liss, Inc.