Genetic Networks Governing Heart Development

Abstract

Animal genomes contain a code for construction of the body plan from a fertilized egg. Understanding how genome information is deciphered to create the complex multilayered regulatory systems that drive organismal development, and which become altered in disease, is one of the greatest challenges in the biological sciences. The development of methods that effectively represent and communicate the complexity inherent in gene regulatory networks remains a major barrier. This review introduces the philosophy of systems biology and discusses recent progress in understanding the development of the heart at a systems biology level. SYSTEMS BIOLOGYS ystems biology is an emerging multidisciplinary field embedded in large-scale data initiatives that seeks to understand the complex interactions occurring within biological systems. The recent increase in popularity of systems biology has been the consequence of technological advances that have flowed from the sequencing of the human genome (Lander et al. 2001). However, the last decade of research has reinforced the notion that to understand biological networks we need to do more than just describe genome organization. A major finding that has reshaped our view of biology is the realization that transcriptional complexity rather than genome size or the number of protein-coding genes is the evolutionary driver for increased biological diversity (Britten and Davidson 1969;Carninci et al. 2005;Fantom Consortium et al. 2014).Network theory hypothesizes that specific interaction patterns in biology have logic and functional significance. The discovery that uni-

Development and evolution of the metazoan heart

“…The differentiation of the precardiac mesoderm in an evolutionary context is driven by interactions between a restricted set of genes. A handful of orthologues (Nkx2.5/Tinman, GATA 4/5/6/Pannier, Hand1/2, Tbx5, Mef2c) in mesodermal precardiac tissues are referred to F I G U R E 1 Phylogenetic relationships to demonstrate the position of arthropods, mollusks, and chordates among the bilaterians and metazoan (After 9 ) as "heart regulatory kernel" 11,22,23 or "core cardiac transcription factors," 24 followed by various sets of "terminal selectors" 25 or "patterning genes," 24 with very different outcomes in ascidians and vertebrates, 26 which can be extended to other taxa such as insects and mollusks. 27 In arthropods, the various types of circulation have recently been described.…”

Embryonic Heart Progenitors and Cardiogenesis

“…SHF progenitors are now gradually added to the looping heart tube and get further restricted in their differentiation potential (E8.5). plex network of spatiotemporal interactions of growth factors and transcriptional regulators (e.g., BMP, Wnt, FGF, Nkx2.5, and Gata4) governs both FHF and SHF development (Kelly 2012;Harvey 2013;Moorman et al 2013). Importantly, ourcurrent knowledge supports a new paradigm for cardiovascular development involving the divergence of myocardial, smooth muscle and endothelial cell lineages from a common precursor.…”

Isoniazid causes heart looping disorder of zebrafish embryo by inducing oxidative stress

“…Therefore, they are prone to external environment and drugs for affecting transcription regulation. The heart is the first organ to form during the embryonic development, including the following stages: the formation of cardiogenic zones from cardiac progenitor cells, with the first cardiogenic zone and the second cardiogenic zone (26,27); the appearance of a linear cardiac tube due to separation and migration of cardiogenic zones at proto-intestinal stage, with heart starting beating; the looping of the linear cardiac tube; the arising of primitive atrium and ventricle structure from endocardial endothelial cells, with undergoing endothelial mesenchymal transformation into endocardial cushions and an ultima heart came into being after cardiac cells remolding (28)(29)(30). Heart development was regulated by a combination of transcription factors, whose down-regulation lead to defects in heart development, teratogenicity and even death of embryos (31).…”