Developmental biology of the vertebrate heart

This paper summarizes the development of the heart from the formation of the heart mesoderm to cardiac septation. A brief account of morphological changes is provided, but attention is focused on mechanisms rather than on morphologic descriptions. Heart induction and differentiation, and the expression of cardiac specific proteins, are reviewed. New developments in these areas include the possible role of cell surface proteins and peptide growth factors in the segregation of the splanchnic mesoderm and in cardiac commitment. Past and recent experiments indicate that the heart morphogenetic information is engraved in the precardiac mesoderm. In spite of this, specific differentiative signals can be overriden experimentally demonstrating the unstability of the cardiac phenotype at the early heart tube stage. The relationship between differentiation and morphogenesis is analyzed. While cardiac differentiation appears to be a prerequisite for morphogenesis, a number of experiments indicate that differentiation can proceed in the absence of any morphogenesis. Formation of the heart loop is separated into two different components; looping itself and the acquisition of handedness. Late heart morphogenesis is explained in terms of differential tissue growth and tissue remodeling. This not only includes morphogenetic changes intrinsic to the heart but the addition of new cell types (neural crest, epicardium, vessels, nerves) that become integrated into the developing heart. The contribution of specific mechanisms to our understanding of heart development, such as cell death and hemodynamics is also analyzed.