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MEF2C is required for the normal allocation of cells between the ventricular and sinoatrial precursors of the primary heart field
Author(s) -
Vong Linh,
Bi Weizhen,
O'ConnorHalligan Katharine E.,
Li Changyou,
Cserjesi Peter,
Schwarz John J.
Publication year - 2006
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20828
Subject(s) - ventricle , mef2c , atrioventricular canal , biology , heart development , medicine , anatomy , microbiology and biotechnology , cardiology , transcription factor , heart disease , gene , genetics , embryonic stem cell
Targeted deletion of the mef2c gene results in a small left ventricle and complete loss of the right ventricle (Lin et al. [1997] Science 276:1404–1407). Absence of the right ventricle is from defective differentiation of cells from the secondary heart field. Our studies of the dysmorphogenesis of the left ventricle uncovered morphological and transcriptional abnormalities at the transition from the cardiac crescent to the linear‐tube stage heart. Use of the cgata6LacZ transgene demonstrated that lacZ ‐positive cells, which normally mark the precursors to the atrioventricular canal and adjacent regions of the left ventricle and atria, remain in the sinoatrial region of the mutant. This, along with the absence of a morphologically distinct atrioventricular canal, indicates a misapportioning of cells between the inflow and outflow segments. The underlying genetic program was also affected with altered expression of mlc2a, mlc2v , and irx4 in outflow segment precursors of the primary heart field. In addition, the sinoatrial‐enriched transcription factor, tbx5 , was ectopically expressed in the primitive ventricle and ventricle‐specific splicing of mef2b was lost, suggesting that the mutant ventricle had acquired atrial‐specific characteristics. Collectively, these results suggest a fundamental role of MEF2C in ventricular cardiomyocyte differentiation and apportioning of cells between inflow and outflow precursors in the primary heart field. Developmental Dynamics 235:1809–1821, 2006. © 2006 Wiley‐Liss, Inc.