Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease.
Sci Rep
; 10(1): 15119, 2020 09 15.
Article
en En
| MEDLINE
| ID: mdl-32934297
ABSTRACT
Most of the gut functions are controlled by the enteric nervous system (ENS), a complex network of enteric neurons located throughout the wall of the gastrointestinal tract. The formation of ENS connectivity during the perinatal period critically underlies the establishment of gastrointestinal motility, but the factors involved in this maturation process remain poorly characterized. Here, we examined the role of Semaphorin 3A (Sema3A) on ENS maturation and its potential implication in Hirschsprung disease (HSCR), a developmental disorder of the ENS with impaired colonic motility. We found that Sema3A and its receptor Neuropilin 1 (NRP1) are expressed in the rat gut during the early postnatal period. At the cellular level, NRP1 is expressed by enteric neurons, where it is particularly enriched at growth areas of developing axons. Treatment of primary ENS cultures and gut explants with Sema3A restricts axon elongation and synapse formation. Comparison of the ganglionic colon of HSCR patients to the colon of patients with anorectal malformation shows reduced expression of the synaptic molecule synapsin 1 in HSCR, which is inversely correlated with Sema3A expression. Our study identifies Sema3A as a critical regulator of ENS connectivity and provides a link between altered ENS connectivity and HSCR.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sinapsinas
/
Colon
/
Sistema Nervioso Entérico
/
Semaforina-3A
/
Enfermedad de Hirschsprung
/
Neuronas
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
/
Infant
/
Male
/
Newborn
Idioma:
En
Revista:
Sci Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM