Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development.
Neuropilin-1 (Npn-1) is a receptor that binds multiple ligands from structurally distinct families, including secreted semaphorins (Sema) and vascular endothelial growth factors (VEGF). We generated npn-1 knockin mice, which express an altered ligand binding site variant of Npn-1, and npn-1 conditional null mice to establish the cell-type- and ligand specificity of Npn-1 function in the developing cardiovascular and nervous systems. Our results show that VEGF-Npn-1 signaling in endothelial cells is required for angiogenesis. In striking contrast, Sema-Npn-1 signaling is not essential for general vascular development but is required for axonal pathfinding by several populations of neurons in the CNS and PNS. Remarkably, both Sema-Npn-1 signaling and VEGF-Npn-1 signaling are critical for heart development. Therefore, Npn-1 is a multifunctional receptor that mediates the activities of structurally distinct ligands during development of the heart, vasculature, and nervous system.
Gu
Chenghua
C
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Rodriguez
E Rene
ER
Reimert
Dorothy V
DV
Shu
Tianzhi
T
Fritzsch
Bernd
B
Richards
Linda J
LJ
Kolodkin
Alex L
AL
Ginty
David D
DD
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001369:Axons / Q000502:physiology; D019556:COS Cells; D002319:Cardiovascular System / Q000196:embryology*; D002522:Chlorocebus aethiops; D003433:Crosses, Genetic; D003712:Dendrites / Q000502:physiology; D016228:Endothelial Growth Factors / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008024:Ligands; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009420:Nervous System / Q000196:embryology*; D039942:Neuropilin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D039961:Semaphorins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D008222:Lymphokines; D039961:Semaphorins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1