title: VEGF189 binds NRP1 and is sufficient for VEGF/NRP1-dependent neuronal patterning in the developing brain.
abstract: The vascular endothelial growth factor (VEGFA, VEGF) regulates neurovascular patterning. Alternative splicing of the Vegfa gene gives rise to three major isoforms termed VEGF121, VEGF165 and VEGF189. VEGF165 binds the transmembrane protein neuropilin 1 (NRP1) and promotes the migration, survival and axon guidance of subsets of neurons, whereas VEGF121 cannot activate NRP1-dependent neuronal responses. By contrast, the role of VEGF189 in NRP1-mediated signalling pathways has not yet been examined. Here, we have combined expression studies and in situ ligand-binding assays with the analysis of genetically altered mice and in vitro models to demonstrate that VEGF189 can bind NRP1 and promote NRP1-dependent neuronal responses.
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Miguel
authors.initials: M
authors.lastname: Tillo
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: Lynda
authors.initials: L
authors.lastname: Erskine
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK University of Milan, Department of Pharmacological and Biomolecular Sciences, Via Balzaretti 9, Milan 20133, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Cariboni
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fantin
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Joyce
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Denti
authors.affiliation: UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK c.ruhrberg@ucl.ac.uk.
authors.forename: Christiana
authors.initials: C
authors.lastname: Ruhrberg
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology*; D017403:In Situ Hybridization; D051379:Mice; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D039942:Neuropilin-1 / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D009841:Oligonucleotides; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D039942:Neuropilin-1
keywords: Mouse; Neuron; Neuropilin; VEGF189; Vascular endothelial growth factor (VEGF)