TY - JOUR
T1 - Semaphorin-PlexinD1 Signaling Limits Angiogenic Potential via the VEGF Decoy Receptor sFlt1
AU - Zygmunt, Tomasz
AU - Gay, Carl Michael
AU - Blondelle, Jordan
AU - Singh, Manvendra K.
AU - Flaherty, Kathleen Mc Crone
AU - Means, Paula Casey
AU - Herwig, Lukas
AU - Krudewig, Alice
AU - Belting, Heinz Georg
AU - Affolter, Markus
AU - Epstein, Jonathan A.
AU - Torres-Vázquez, Jesús
N1 - Funding Information:
We thank N.C. Chi, C-B. Chien, S. Childs, A. Chitnis, S.L. Johnson, K. Kawakami, N.D. Lawson, M. Parsons, S. Schulte-Merker, D. Stainier, B.M. Weinstein, and the Zebrafish International Resource Center for reagents; G. Fishell, E.J.A. Hubbard, H. Knaut, J.F. Nance, D.B. Rifkin, K.L. Targoff, J.E. Treisman, S.R. Schwab, F. Ulrich, K.A. Yaniv, and D. Yelon for discussions; J. Zavadil (NYU Cancer Institute Genomics Facility), D. Dalfo, and J.-Y. Roignant for qPCR advice; and D. Chan for administrative help. We were supported by Werner Siemens-Foundation, Switzerland (A.K.), NICHD Training Program grant 5T32HD007520-05 (C.M.G.), and The David Himelberg Foundation and NHLBI (J.T.-V.). Author breakdown is as follows: T.Z., C.M.G., J.T.-V. (ideas, experiments, data analysis, fish lines, plasmids, writing); J.B., P.C.M. (experiments, data analysis); K.M.F. (experiments, fish lines, husbandry support, writing); M.K.S. (ideas, cell culture experiments, data analysis, writing); L.H., A.K., H.-G.B., M.A. ( Tg(fliep:gal4ff) ubs4 line); J.A.E. (ideas, data analysis). All authors commented on the manuscript.
PY - 2011/8/16
Y1 - 2011/8/16
N2 - Sprouting angiogenesis expands the embryonic vasculature enabling survival and homeostasis. Yet how the angiogenic capacity to form sprouts is allocated among endothelial cells (ECs) to guarantee the reproducible anatomy of stereotypical vascular beds remains unclear. Here we show that Sema-PlxnD1 signaling, previously implicated in sprout guidance, represses angiogenic potential to ensure the proper abundance and stereotypical distribution of the trunk's segmental arteries (SeAs). We find that Sema-PlxnD1 signaling exerts this effect by antagonizing the proangiogenic activity of vascular endothelial growth factor (VEGF). Specifically, Sema-PlxnD1 signaling ensures the proper endothelial abundance of soluble flt1 (sflt1), an alternatively spliced form of the VEGF receptor Flt1 encoding a potent secreted decoy. Hence, Sema-PlxnD1 signaling regulates distinct but related aspects of angiogenesis: the spatial allocation of angiogenic capacity within a primary vessel and sprout guidance.
AB - Sprouting angiogenesis expands the embryonic vasculature enabling survival and homeostasis. Yet how the angiogenic capacity to form sprouts is allocated among endothelial cells (ECs) to guarantee the reproducible anatomy of stereotypical vascular beds remains unclear. Here we show that Sema-PlxnD1 signaling, previously implicated in sprout guidance, represses angiogenic potential to ensure the proper abundance and stereotypical distribution of the trunk's segmental arteries (SeAs). We find that Sema-PlxnD1 signaling exerts this effect by antagonizing the proangiogenic activity of vascular endothelial growth factor (VEGF). Specifically, Sema-PlxnD1 signaling ensures the proper endothelial abundance of soluble flt1 (sflt1), an alternatively spliced form of the VEGF receptor Flt1 encoding a potent secreted decoy. Hence, Sema-PlxnD1 signaling regulates distinct but related aspects of angiogenesis: the spatial allocation of angiogenic capacity within a primary vessel and sprout guidance.
UR - http://www.scopus.com/inward/record.url?scp=79961236169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79961236169&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2011.06.033
DO - 10.1016/j.devcel.2011.06.033
M3 - Article
C2 - 21802375
AN - SCOPUS:79961236169
SN - 1534-5807
VL - 21
SP - 301
EP - 314
JO - Developmental cell
JF - Developmental cell
IS - 2
ER -