Ccbe1 expression marks the cardiac and lymphatic progenitor lineages during early stages of mouse development.

The mammalian heart is a complex organ composed of diverse components and various cell types. Heart organogenesis requires the contribution of distinct pools of heart progenitors positioned in separate embryonic regions and subject to particular developmental signals. Moreover, these embryonic heart lineages have different transcriptional profiles expressing specific genes which activate pathways involved in heart lineage specification. Understanding the molecular control of heart organogenesis has major implications for treating congenital and adult heart diseases since specific heart lineages have been associated with particular human cardiovascular malformations. Collagen and calcium-binding EGF-like domain 1 (Ccbe1) was identified in our laboratory using an Affymetrix GeneChip system approach to identify the transcriptome of chick heart/hemangioblast precursor cells. Here, we present a detailed and systematic analysis of the expression of Ccbe1 during early mouse development using whole-mount in situ hybridization (WISH), immunohistochemistry and histological techniques. Ccbe1 mRNA was initially detected in the early cardiac progenitors of the two bilateral cardiogenic fields (E7.0) and in the cardiogenic mesoderm (E7.5 to E8.0). Ccbe1 mRNA was then persistently detected in the pericardium and transiently expressed in the myocardial tissue of the primitive heart tube (E8.25), being later expressed in the proepicardium. By E9.5, the Ccbe1 and Prox1 proteins were found to be expressed in common regions, including the septum transversum and in the proximity of the anterior cardinal vein. Here, it is shown that Ccbe1 is expressed in the FHF, SHF and proepicardium during heart organogenesis (E7.0 to E8.75). Later in development, Ccbe1 expression is localized in the septum transversum and in the vicinity of the anterior cardinal vein, embryonic structures related to hepatic and lymphatic development, respectively.