A common Shox2-Nkx2-5 antagonistic mechanism primes the pacemaking cell fate in the pulmonary vein myocardium and sinoatrial node
نویسندگان
چکیده
منابع مشابه
Dev120220 2521..2532
In humans, atrial fibrillation is often triggered by ectopic pacemaking activity in the myocardium sleeves of the pulmonary vein (PV) and systemic venous return. The genetic programs that abnormally reinforce pacemaker properties at these sites and how this relates to normal sinoatrial node (SAN) development remain uncharacterized. It was noted previously that Nkx2-5, which is expressed in the ...
متن کاملGenetic Regulation of Sinoatrial Node Development and Pacemaker Program in the Venous Pole
The definitive sinoatrial node (SAN), the primary pacemaker of the mammalian heart, develops from part of pro-pacemaking embryonic venous pole that expresses both Hcn4 and the transcriptional factor Shox2. It is noted that ectopic pacemaking activities originated from the myocardial sleeves of the pulmonary vein and systemic venous return, both derived from the Shox2+ pro-pacemaking cells in th...
متن کاملTargeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development.
BACKGROUND Identifying molecular pathways regulating the development of pacemaking and coordinated heartbeat is crucial for a comprehensive mechanistic understanding of arrhythmia-related diseases. Elucidation of these pathways has been complicated mainly by an insufficient definition of the developmental structures involved in these processes and the unavailability of animal models specificall...
متن کاملPitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium.
The pulmonary vein is sleeved by myocardium, which is a major source of atrial fibrillation and is involved in congenital sinus venosus defects. Little is known about the cellular origin and mechanism of formation of the pulmonary myocardium. We observed a biphasic process of pulmonary myocardium formation in mice. Firstly, a myocardial cell population forms de novo at the connection of the pul...
متن کاملDynamical description of sinoatrial node pacemaking: improved mathematical model for primary pacemaker cell.
We developed an improved mathematical model for a single primary pacemaker cell of the rabbit sinoatrial node. Original features of our model include 1) incorporation of the sustained inward current (I(st)) recently identified in primary pacemaker cells, 2) reformulation of voltage- and Ca(2+)-dependent inactivation of the L-type Ca(2+) channel current (I(Ca,L)), 3) new expressions for activati...
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ژورنال
عنوان ژورنال: Development
سال: 2015
ISSN: 1477-9129,0950-1991
DOI: 10.1242/dev.120220