A retrospective clonal analysis of the myocardium reveals two phases of clonal growth in the developing mouse heart
2003
Key molecules which regulate the formation of the heart have been
identified; however, the mechanism of cardiac morphogenesis remains poorly
understood at the cellular level. We have adopted a genetic approach, which
permits retrospective clonal analysis of myocardial cells in the mouse embryo,
based on the targeting of an nlaacZ reporter to the α-cardiac
actin gene. A rare intragenic recombination event leads to a clone ofβ
-galactosidase-positive myocardial cells. Analysis of clones at
different developmental stages demonstrates that myocardial cells and their
precursors follow a proliferative mode of growth, rather than a stem cell
mode, with an initial dispersive phase, followed by coherent cell growth.
Clusters of cells are dispersed along the venous-arterial axis of the heart
tube. Coherent growth is oriented locally, with a main axis, which corresponds
to the elongation of the cluster, and rows of cells, which form secondary
axes. The angle between the primary and secondary axes varies, indicating
independent events of growth orientation. At later stages, as the ventricular
wall thickens, wedge shaped clusters traverse the wall and contain rows of
cells at a progressive angle to each other. The cellular organisation of the
myocardium appears to prefigure myofibre architecture. We discuss how the
characteristics of myocardial cell growth, which we describe, underlie the
formation of the heart tube and its subsequent regionalised expansion.
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