Morphological and molecular left–right asymmetries in the development of the proepicardium: A comparative analysis on mouse and chick embryos

Abstract

The proepicardium (PE) is an embryonic progenitor cell population that delivers the epicardium, the majority of the cardiac interstitium, and the coronary vasculature. In the present study, we compared PE development in mouse and chick embryos. In the mouse, a left and a right PE anlage appear simultaneously, which subsequently merge at the embryonic midline to form a single PE. In chick embryos, the right PE anlage appears earlier than the left and only the right anlage acquires the full PE-phenotype. The left anlage remains in a rudimentary state. The expression patterns of PE marker genes (Tbx18, Wt1) correspond to the morphological data, being bilateral in the mouse and unilateral in the chick. Bmp4, which is unilaterally expressed in the right PE of chick embryos, is symmetrically expressed in the sinus venosus wall cranial to the PE in mouse embryos. Asymmetric development of the chicken PE might reflect side-specific differences in topographical relationships to tissues with PE-inducing or repressing activity or might result from the PE-repressing activity of the right PE, which grows earlier. To test these hypotheses, we analyzed PE development in chick embryos, firstly, subsequent to experimentally induced inversion of PE topographical relationships to neighbouring tissues; secondly, in organ cultures; and, thirdly, subsequent to induction of cardia bifida. In all three experiments, only the right PE develops the full PE phenotype. Our results suggest that PE development might be controlled by the L-R pathway in the chick but not in the mouse embryo.

The Development of the Epicardium in the Sturgeon Acipenser naccarii

“…However, it is consistent with the bilateral expression of several PE marker genes in the early sinus horn of the chick (Schlueter et al, 2006), and with the origin of the PE from the right horn of the sinus venosus in Xenopus (Jahr et al, 2008). In elasmobranches, birds, and mammals, the PE appears as a bilateral structure (Muñ oz-Chá puli et al, 1994;Mä nner et al, 2001;Schulte et al, 2007) that undergoes a process of fusion. The same occurs in the sturgeon indicating, as observed in the zebrafish (Serluca, 2008), a double PE origin from progenitors located in the lateral plate mesoderm.…”

“…On the other hand, the form and extent of the PE vary between species (Mä nner et al, 2001). Although the semilunar shape of the PE appears to be specific to the sturgeon, it has been described as triangular in the mouse embryo (Schulte et al, 2007). Species differences also exist in the histologic appearance of the PE villi.…”

A right-sided pathway involving FGF8 / Snai1 controls asymmetric development of the proepicardium in the chick embryo

“…Tbx18 expression was used throughout our experiments as a PE-specific marker gene (22,23). At Hamburger Hamilton (HH) stage 12 and 13, a Tbx18 expression domain was found on the right sinus horn but was absent on the left sinus horn [supporting information (SI) Fig.…”

“…The PE cells colonize the developing heart via the formation of a secondary tissue bridge and differentiate into a variety of cell types including the epicardium, the cardiac interstitium, and the coronary vasculature (20). In the chick and frog embryo, the PE only forms on the right side of the embryo (21)(22)(23). Therefore, in these species several PE-marker genes normally display a bilaterally asymmetric expression, being strongly expressed on the right and only weakly on the left side (23).…”

“…Therefore, in these species several PE-marker genes normally display a bilaterally asymmetric expression, being strongly expressed on the right and only weakly on the left side (23). The vestigial PE that forms on the left body side ultimately undergoes apoptosis and never establishes contact to the heart (22).…”