Gene regulatory networks for the development and evolution of the chordate heart

Gene regulatory networks consisting of subcircuits of transcription factors and intercellular signaling molecules are key to an understanding of the complex mechanisms of animal development and evolution (Davidson and Erwin 2006). One of the most intensively studied genetic networks is that for the formation of the animal heart. Since the discovery of the “tinman” gene (Bodmer 1993) and its vertebrate homolog, Nkx2.5 (Lyons et al. 1995), many genes have been found to be involved in heart development in a wide range of animals, from insects to mammals. Actually, it is well established that a gene circuit consisting of GATA, Nkx, and Hand is evolutionarily highly conserved. This gene circuit constitutes a “kernel,” which is evolutionarily inflexible and performs essential regulatory functions in building a body part (Davidson and Erwin 2006). Analyses of vertebrate heart development revealed that the differentiation of cardiac muscle cells and morphogenesis of the heart are governed by this heart kernel gene regulatory network (Cripps and Olson 2002; Harvey 2002; Buckingham et al. 2005). An important question to be answered about the formation of the heart in vertebrates and other chordates is how this kernel is turned on at the earliest stages of the heart cell specification process to establish the heart field.

Another intriguing question in chordate heart formation is how the dual- or multichambered heart of vertebrates evolved. It is generally believed that the ancestral chordate resembled the present-day ascidian tadpole. The morphogenetic movement of heart precursor cells during ascidian larval development and metamorphosis is reminiscent of those in vertebrates (Davidson and Levine 2003). However, the ascidian tube-like heart lacks chambers. The innovation of the chambered heart was a key event in vertebrate evolution, because the chambered heart generates one-way blood flow with high pressure, a critical requirement for …