“…In one study (Pennisi et al, 2003) in which interference with epicardium formation in chick embryos led to a clearly evident ventricular wall phenotype, there was only an 11% reduction in proliferation rate as measured by BrdU incorporation; however, clonal analysis revealed the loss of one cycle of cell division, and those authors emphasized that one fewer round of cell division over a period of a few days would result in a 50% reduction in compact zone thickness. In experimental models with severe compact zone thinning, the extent to which compact zone proliferation is decreased does not exceed 50% (Kastner et al, 1997;Bushdid et al, 2003) and, in more typical cases, still with dramatic compact zone hypoplasia, reductions in the range of 30-45% were seen (Lavine et al, 2005;Zamora et al, 2007;Lavine et al, 2008;Nanka et al, 2008;Peng et al, 2008). IGF signaling deficiency has a phenotypic impact of this magnitude (Fig.…”