Early signals in cardiac development

The heart is the first organ to form during embryogenesis and its circulatory function is critical from early on for the viability of the mammalian embryo. Developmental abnormalities of the heart have also been widely recognized as the underlying cause of many congenital heart malformations. Hence, the developmental mechanisms that orchestrate the formation and morphogenesis of this organ have received much attention among classical and molecular embryologists. Due to the evolutionary conservation of many of these processes, major insights have been gained from the studies of a number of vertebrate and invertebrate models, including mouse, chick, amphibians, zebrafish, and Drosophila. In all of these systems, the heart precursors are generated within bilateral fields in the lateral mesoderm and then converge toward the midline to form a beating linear heart tube. The specification of heart precursors is a result of multiple tissue and cell-cell interactions that involve temporally and spatially integrated programs of inductive signaling events. In the present review, we focus on the molecular and developmental functions of signaling processes during early cardiogenesis that have been defined in both vertebrate and invertebrate models. We discuss the current knowledge on the mechanisms through which signals induce the expression of cardiogenic transcription factors and the relationships between signaling pathways and transcriptional regulators that cooperate to control cardiac induction and the formation of a linear heart tube.