Semaphorin3A, Neuropilin-1, and PlexinA1 are required for lymphatic valve formation.
Circ Res
; 111(4): 437-45, 2012 Aug 03.
Article
en En
| MEDLINE
| ID: mdl-22723296
ABSTRACT
RATIONALE The lymphatic vasculature plays a major role in fluid homeostasis, absorption of dietary lipids, and immune surveillance. Fluid transport depends on the presence of intraluminal valves within lymphatic collectors. Defective formation of lymphatic valves leads to lymphedema, a progressive and debilitating condition for which curative treatments are currently unavailable. How lymphatic valve formation is regulated remains largely unknown. OBJECTIVE:
We investigated if the repulsive axon guidance molecule Semaphorin3A (Sema3A) plays a role in lymphatic valve formation. METHODS ANDRESULTS:
We show that Sema3A mRNA is expressed in lymphatic vessels and that Sema3A protein binds to lymphatic valves expressing the Neuropilin-1 (Nrp1) and PlexinA1 receptors. Using mouse knockout models, we show that Sema3A is selectively required for lymphatic valve formation, via interaction with Nrp1 and PlexinA1. Sema3a(-/-) mice exhibit defects in lymphatic valve formation, which are not due to abnormal lymphatic patterning or sprouting, and mice carrying a mutation in the Sema3A binding site of Nrp1, or deficient for Plxna1, develop lymphatic valve defects similar to those seen in Sema3a(-/-) mice.CONCLUSIONS:
Our data demonstrate an essential direct function of Sema3A-Nrp1-PlexinA1 signaling in lymphatic valve formation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Superficie Celular
/
Semaforina-3A
/
Neuropilina-1
/
Vasos Linfáticos
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Guideline
/
Prognostic_studies
Idioma:
En
Revista:
Circ Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia