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

Chappell, John C.Darden, JordanPayne, Laura BethFink, KathrynBautch, Victoria L.2019-09-232019-09-232019-09-07Chappell, J.C.; Darden, J.; Payne, L.B.; Fink, K.; Bautch, V.L. Blood Vessel Patterning on Retinal Astrocytes Requires Endothelial Flt-1 (VEGFR-1). J. Dev. Biol. 2019, 7, 18.http://hdl.handle.net/10919/93969Feedback 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 flt-1 differentially affects the branching complexity of vascular networks in tissues despite similar effects on endothelial sprouting. We selectively ablated flt-1 in the post-natal retina and found that maximum induction of flt-1 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 flt-1 revealed that sprouting endothelial cells flanked by flt-1−/− 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 flt-1-regulated angiogenic molecular and cellular mechanisms to yield optimal vessel patterning for a given tissue.application/pdfenCreative Commons Attribution 4.0 Internationalflt-1VEGF-Aangiogenesisretinablood vessel developmentBlood Vessel Patterning on Retinal Astrocytes Requires Endothelial Flt-1 (VEGFR-1)Article - Refereed2019-09-23Journal of Developmental Biologyhttps://doi.org/10.3390/jdb7030018