Blood vessels and neurons share guidance cues and cell-surface receptors to control their behaviour during embryogenesis. The transmembrane protein NRP1 (neuropilin 1) is present on both blood vessels and nerves and binds two structurally diverse ligands, the class 3 semaphorin SEMA3A and an isoform of the vascular endothelial growth factor VEGF-A termed VEGF165 (VEGF164 in mice). In vitro, SEMA3A competes with VEGF164 for binding to NRP1 to modulate the migration of endothelial cells and neuronal progenitors. It was therefore hypothesized that NRP1 signalling controls neurovascular co-patterning by integrating competing VEGF164 and SEMA3A signals. However, SEMA3A, but not VEGF164, is required for axon patterning of motor and sensory nerves, and, vice versa, VEGF164 rather than SEMA3A is required for blood vessel development. Ligand competition for NRP1 therefore does not explain neurovascular congruence. Instead, these ligands control different aspects of neurovascular patterning that have an impact on cardiovascular function. Thus SEMA3A/NRP1 signalling guides the NCC (neural crest cell) precursors of sympathetic neurons as well as their axonal projections. In addition, VEGF164 and a second class 3 semaphorin termed SEMA3C contribute to the remodelling of the embryonic pharyngeal arch arteries and primitive heart outflow tract by acting on endothelium and NCCs respectively. Consequently, loss of either of these NRP1 ligands disrupts blood flow into and out of the heart. Multiple NRP1 ligands therefore co-operate to orchestrate cardiovascular morphogenesis.
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December 2009
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Conference Article|
November 19 2009
Neuropilin ligands in vascular and neuronal patterning
Alessandro Fantin;
Alessandro Fantin
1UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, U.K.
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Charlotte H. Maden;
Charlotte H. Maden
1UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, U.K.
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Christiana Ruhrberg
Christiana Ruhrberg
1
1UCL Institute of Ophthalmology, 11–43 Bath Street, London EC1V 9EL, U.K.
1To whom correspondence should be addressed (email c.ruhrberg@ucl.ac.uk).
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Biochem Soc Trans (2009) 37 (6): 1228–1232.
Article history
Received:
August 28 2009
Citation
Alessandro Fantin, Charlotte H. Maden, Christiana Ruhrberg; Neuropilin ligands in vascular and neuronal patterning. Biochem Soc Trans 1 December 2009; 37 (6): 1228–1232. doi: https://doi.org/10.1042/BST0371228
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