Abstract 1462: Lineage Analysis of Mesp1 Expressing Cells in Cardiac Conduction System

Abstract

Mesp1 is the earliest transcription factor detected in cardiac precursor cells considered to play a key role in their early specification. The lineage analysis, using Mesp1- Cre transgenic mouse line, has shown that there is a minor contribution of Mesp1 non-expressing cells to the formation of ventricular conduction system. The purpose of the present study is to evaluate the contribution of Mesp1 -expressing and non-expressing cells to the development of sinoatrial node, atrioventricular node and His bundle in embryonic, neonatal and adult heart. In this study, the contribution of Mesp1 -expressing cells was evaluated by a lineage analysis using the cross of Mesp1 -Cre and ROSA26R reporter mice. Different components of the cardiac conduction system were identified by a combination of histological (hematoxylin/eosin), acetylcholinesterase, and immunofluorescent stainings for specific markers (HCN4 and connexin40). Sinoatrial and atrioventricular nodes as well as His bundle are derived almost exclusively from Mesp1- expressing cells as evident by β-gal activity. The contribution of Mesp1 non-expressing cells becomes prominent, though still less than Mesp1 -expressing cells, in the distal components of cardiac conduction system (i.e. bundle branches). This pattern was consistent in embryonic and neonatal stages as well as adult hearts. Unlike the distal components of cardiac conduction system, which is composed of a mixed population of Mesp1 -expressing and non-expressing cells, sinoatrial node, atrioventricular node and His bundle are derived almost exclusively from Mesp1 -expressing cells.