Blood Vessel Patterning on Retinal Astrocytes Requires Endothelial Flt-1 (VEGFR-1).

Feedback mechanisms are critical components of many pro-angiogenic signaling pathways that keep vessel growth within a functional range. The Vascular Endothelial Growth Factor-A (VEGF-A) pathway utilizes the decoy VEGF-A receptor Flt-1 to provide negative feedback regulation of VEGF-A signaling. In this study, we investigated how the genetic loss of differentially affects the branching complexity of vascular networks in tissues despite similar effects on endothelial sprouting. We selectively ablated in the post-natal retina and found that maximum induction of loss resulted in alterations in endothelial sprouting and filopodial extension, ultimately yielding hyper-branched networks in the absence of changes in retinal astrocyte architecture. The mosaic deletion of revealed that sprouting endothelial cells flanked by regions of vasculature more extensively associated with underlying astrocytes and exhibited aberrant sprouting, independent of the tip cell genotype. Overall, our data support a model in which tissue patterning features, such as retinal astrocytes, integrate with -regulated angiogenic molecular and cellular mechanisms to yield optimal vessel patterning for a given tissue.