The morphology and physiology of the heart have fascinated scientists for decades. Nevertheless, the molecular pathways regulating heart formation are still poorly understood, especially in the context of congenital heart disease (CHD). The heart is the first organ to develop, and the looping of the heart to the right during embryonic development is the first morphological instance in which the bilateral symmetry of the embryo is altered. Many of the mechanical problems manifest in CHD arise from structures which are missing, or structures which are malformed and hence malfunction. In many cases these defects can ultimately be seen as derived from problems in proper establishment of laterality, such as looping morphogenesis defects. Here, we propose to look for novel genes involved in heart development, and particularly for those involved in the determination of cardiac left-right asymmetry. Toward this end, we will utilize mice in which the cells of the cardiac primordium (which express the gene Nkx2.5) are marked with a fluorescent tag (GFP). We will microsurgically remove the left and right halves of Nkx2.5-GFP mouse embryos at 7.5 dpc and use FACS to screen for cells that express the Nkx2.5-GFP reporter gene. Then, we will prepare fluorescent cDNA libraries from the left and right halves of the embryos and use these cDNA pools as probes to screen a heart cDNA library gridded on microarrays.
| Rivera-Feliciano, Jose; Lee, Kyu-Ho; Kong, Sek Won et al. (2006) Development of heart valves requires Gata4 expression in endothelial-derived cells. Development 133:3607-18 |
| Rivera-Feliciano, Jose; Tabin, Clifford J (2006) Bmp2 instructs cardiac progenitors to form the heart-valve-inducing field. Dev Biol 295:580-8 |
