GATA4 in Heart Development and Disease

This chapter discusses the role of GATA4 in the heart development and disease. GATA proteins are expressed in a cell- and temporal-specific manner. Their essential roles in early development are well established and include lineage differentiation, as well as cell survival and proliferation. For example, in plants, GATA proteins are involved in flower development, whereas in C. elegans, fish and mammals, the different GATA proteins are crucial for lineage specification and organ development. This is well characterized in C. elegans, where the Elt and END proteins are involved in the commitment of cells into the endodermal lineage whereas the MED proteins are involved in specification of the mesendodermal cells. This role in lineage commitment is crucial for the evolution of metazoans, where compartmentalization via cell layer formation is a major event. GATA proteins also play essential roles throughout the lifecycle of the various organisms as they act as sensor/effectors of external threats and stimuli, and thus contribute to the inner defense mechanism of the cell. This particular role is conserved during evolution from fungi to higher vertebrates. For example, a protein plays an essential role in nitrogen metabolism in Aspergillus nidulans (Wilson and Arst Jr, 1998), and GATA proteins NIL1 and GLN3 are crucial regulators of carbon and nitrogen metabolism in Saccharomyces cerevisiae (Kuruvilla et al., 2001). As will be discussed in this chapter, mammalian GATA proteins play an important role in cardiac stress responses, and are critical regulators of cell survival.