The chick embryo as an expanding experimental model for cancer and cardiovascular research

Abstract

A long and productive history in biomedical research defines the chick as a model for human biology. Fundamental discoveries, including the description of directional circulation propelled by the heart and the link between oncogenes and the formation of cancer, indicate its utility in cardiac biology and cancer. Despite the more recent arrival of several vertebrate and invertebrate animal models during the last century, the chick embryo remains a commonly used model for vertebrate biology and provides a tractable biological template. With new molecular and genetic tools applied to the avian genome, the chick embryo is accelerating the discovery of normal development and elusive disease processes. Moreover, progress in imaging and chick culture technologies is advancing real-time visualization of dynamic biological events, such as tissue morphogenesis, angiogenesis, and cancer metastasis. A rich background of information, coupled with new technologies and relative ease of maintenance, suggest an expanding utility for the chick embryo in cardiac biology and cancer research.

Keywords: cancer metastasis; cardiac development; cell motility; chick CAM; chick model history; chicken embryo; in vivo imaging.

Figure 1. A) Chick embryo staging and the experimental timeline

A developmental timeline of the chick embryo in days is matched with the Hamburger-Hamilton stages using selected images (Hamburger and Hamilton, 1951) and time-matched images from ex ovo culture. Common experimental models are matched to the time line shown at the top. B) Whole mount of E6 embryo. Dotted line indicates approximate transected views shown in C-E. C) H&E staining of transverse section taken from E6 embryo. Developing structures in heart (D) were visualized using immunofluorescent staining with matching H&E staining (E) respectively.

Figure 2. Tumor xenografting onto the chick CAM

Images demonstrate in ovo (left column) and ex ovo (right column) xenograft models of the CAM. Tumor cells grafted in ovo can be harvested for traditional procession. Tumors grafted ex ovo are more readily accessible for in situ analysis including direct observation through intravital imaging (bottom right).

Figure 3. Modeling angiogenesis in the chick CAM

A day 13 chick embryo bearing 4 angiogenesis onplants is shown. The insets show a control onplant that lacks angiogenic growth factors and an angiogenic onplant that contains both Vascular Endothelial Cell Growth Factor (VEGF) and Basic Fibroblast Growth Factor (FGFb).