A recent study initiated in 1981, the Baltimore-Washington Infant study, is a case-control analysis of congenital cardiovascular anomalies. This study underscores the increasing awareness that susceptibility to cardiovascular abnormalities in terms of the cellular, molecular, and biochemical events is based upon developmental processes which form the subjects of fundamental research in morphology, embryology and genetics. Currently, however, there is still little known about the fundamental cellular and molecular processes that form the heart. Cell interactions are important in the regulation of cell growth, the migration of cells, differentiation, and in the assembly of cells into multicellular tissues and organisms. In the development of the heart, as in many other organ systems, all of these developmental processes play an important role. My research indicates that N-cadherin, a calcium-dependent cell adhesion molecule, has an important morphoregulatory role during stages of early heart development. It appears to be involved in delineation and epithelialization of the precardiac mesoderm cell population and in pericardial coelom formation. Right after these events occur, myofibrillogenesis is first detected, as well as electrical activity in the heart forming regions. Thus, this molecule may be involved in a crucial time period during which the cardiomyocyte appears to be committed and is followed by phenotypic differentiation.These events have little been studied in molecular or biochemical detail. This grant proposes:.(1) to analyze N-cadherin's interaction with intracellular proteins during early heart development using immunoprecipitation experiments, Western blots, and immunohistochemical localization; (2) to ascertain a causal relationship of N-cadherin localization to regulatory events in early heart development by perturbing normal interactions using N-cadherin and catenin antibodies or oliognucleotides; (3) to define N-cadherin gene expression spatio-temporally in the heart forming region using in situ hybridization analyses; and (4) to determine whether a link exists between precardiac cell epithelialization, Na/K-ATPase polar expression, and pericardial coelom development using ouabain to inhibit Na/K-ATPase activity. Cadherins are generally accepted as playing important roles during embryonic development. However, no studies that I am aware of have been carried out to analyze N-cadherin's possible regulatory role during pericardial coelom development and in the establishment of precardiomyogenetic commitment and differentiation.
| Linask, Kaari L; Linask, Kersti K (2010) Calcium channel blockade in embryonic cardiac progenitor cells disrupts normal cardiac cell differentiation. Stem Cells Dev 19:1959-65 |
