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 VEGF(165) (VEGF(164) in mice). In vitro, SEMA3A competes with VEGF(164) 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 VEGF(164) and SEMA3A signals. However, SEMA3A, but not VEGF(164), is required for axon patterning of motor and sensory nerves, and, vice versa, VEGF(164) 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, VEGF(164) 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.

Neuropilin ligands in vascular and neuronal patterning / A. Fantin, C. Maden, C. Ruhrberg. - In: BIOCHEMICAL SOCIETY TRANSACTIONS. - ISSN 0300-5127. - 37:6(2009), pp. 1228-1232.

Neuropilin ligands in vascular and neuronal patterning

A. Fantin
Primo
;
2009

Abstract

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 VEGF(165) (VEGF(164) in mice). In vitro, SEMA3A competes with VEGF(164) 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 VEGF(164) and SEMA3A signals. However, SEMA3A, but not VEGF(164), is required for axon patterning of motor and sensory nerves, and, vice versa, VEGF(164) 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, VEGF(164) 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.
blood vessel; neural crest; neuron; neuropilin; semaphorin; vascular endothelial growth factor (VEGF)
Settore BIO/06 - Anatomia Comparata e Citologia
Settore BIO/09 - Fisiologia
Settore BIO/13 - Biologia Applicata
Settore BIO/17 - Istologia
Article (author)
File in questo prodotto:
File Dimensione Formato  
rev 2009.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 211.68 kB
Formato Adobe PDF
211.68 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/656787
Citazioni
  • ???jsp.display-item.citation.pmc??? 21
  • Scopus 43
  • ???jsp.display-item.citation.isi??? 38
social impact