Abstract
Genes required for an organism to develop to maturity (for which no other gene can compensate) are considered essential. The continuing functional annotation of the mouse genome has enabled the identification of many essential genes required for specific developmental processes including cardiac development. Patterns are now emerging regarding the functional nature of genes required at specific points throughout gestation. Essential genes required for development beyond cardiac progenitor cell migration and induction include a small and functionally homogenous group encoding transcription factors, ligands and receptors. Actions of core cardiogenic transcription factors from the Gata, Nkx, Mef, Hand, and Tbx families trigger a marked expansion in the functional diversity of essential genes from midgestation onwards. As the embryo grows in size and complexity, genes required to maintain a functional heartbeat and to provide muscular strength and regulate blood flow are well represented. These essential genes regulate further specialization and polarization of cell types along with proliferative, migratory, adhesive, contractile, and structural processes. The identification of patterns regarding the functional nature of essential genes across numerous developmental systems may aid prediction of further essential genes and those important to development and/or progression of disease. genesis 52:713–737, 2014.
Highlights
Alteration or deletion of genes is a valuable methodology to determine gene function
During the first stages of cardiac development, after gastrulation, at embryonic day (E) 6.5–7.5, cardiac progenitors from the anterior mesodermal primitive streak migrate anteriorly and laterally on either side of the embryonic midline (Fig. 1A) (Tam and Behringer, 1997; Tam et al, 1997); primary heart field (PHF) cells are derived from these cells
This was originally thought to be entirely from the PHF, LacZ transgene expression under Fgf10 promoter control in mice revealed contributions of a second heart field (SHF) to the outflow tract (OFT) myocardium, with transgene expression originating in the pharyngeal mesoderm from E7.5 (Kelly et al, 2001)
Summary
Alteration or deletion of genes is a valuable methodology to determine gene function. Genes absolutely required for an organism to develop to maturity and for which there is no compensation for critical aspects of their function are considered essential. Less consideration has been paid to the functional diversity of genes that are essential to specific developmental processes and the temporal requirements for differential functions. Many genes involved in mammalian cardiac development are essential, due to the requirement for cardiac function in utero early during gestation. Examples of genes essential to cardiac development at different stages or in specific processes will be detailed, and their roles analyzed to present a composite of the functional diversity of cardiac essential genes. Some of the processes required in cardiogenesis are needed in embryogenesis in general, so cardiac essential genes may affect the development of the early embryo or other organ systems. This review predominantly covers genes and genetic pathways specific to cardiogenesis
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