| First Author | Chappell JC | Year | 2019 |
| Journal | J Dev Biol | Volume | 7 |
| Issue | 3 | PubMed ID | 31500294 |
| Mgi Jnum | J:282463 | Mgi Id | MGI:6378792 |
| Doi | 10.3390/jdb7030018 | Citation | Chappell JC, et al. (2019) Blood Vessel Patterning on Retinal Astrocytes Requires Endothelial Flt-1 (VEGFR-1). J Dev Biol 7(3) |
| abstractText | 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 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. |
