RHOA-ROCK signalling is necessary for lateralization and differentiation of the developing sinoatrial node.
Cardiovasc Res
; 113(10): 1186-1197, 2017 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-28899000
ABSTRACT
AIMS:
RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN. The aim of this study is to assess the role of RHOA-ROCK signalling in SAN development in the chicken heart. METHODS ANDRESULTS:
ROCK signalling was inhibited chemically in embryonic chicken hearts using Y-27632. This prolonged the immature state of the sinus venosus myocardium, evidenced by up-regulation of the transcription factor ISL1, wide distribution of pacemaker potential, and significantly reduced heart rate. Furthermore ROCK inhibition caused aberrant expression of typical SAN genes ROCK1, ROCK2, SHOX2, TBX3, TBX5, ISL1, HCN4, CX40, CAV3.1, and NKX2.5 and left-right asymmetry genes PITX2C and NODAL. Anatomical abnormalities in pulmonary vein development were also observed. Patch clamp electrophysiology confirmed the immature phenotype of the SAN cells and a residual left-sided sinus venosus myocardium pacemaker-like potential.CONCLUSIONS:
RHOA-ROCK signalling is involved in establishing the right-sided SAN as the definitive pacemaker of the heart and restricts typical pacemaker gene expression to the right side of the sinus venosus myocardium.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nodo Sinoatrial
/
Relojes Biológicos
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Transducción de Señal
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Diferenciación Celular
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Proteína de Unión al GTP rhoA
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Quinasas Asociadas a rho
Límite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Año:
2017
Tipo del documento:
Article
País de afiliación:
Países Bajos