TBX20

TBX20 (gene) is a member of the is_associated_with::T-box family that encodes the transcription factor TBX20. Studies in mouse, human and fruitfly have shown that this gene is essential for early heart development,   adult heart function and is_associated_with::yolk sac is_associated_with::vasculature remodeling and has been associated with congenital heart diseases. Tbx20 was also shown to be required for migration of is_associated_with::hindbrain is_associated_with::motor neurons and in facial neurons was proposed to be a positive regulator of the non-canonical is_associated_with::Wnt signaling pathway.

Tbx20 is a is_associated_with::transcription factor that is essential for proper heart development in a growing is_associated_with::fetus. Any mutations in this gene can result in various forms of is_associated_with::congenital heart disease. One of the more serious examples is the presence of a is_associated_with::septal defect. The is_associated_with::interatrial septum is a piece of tissue that separates the left and right atria of the heart, which contain oxygenated and deoxygenated blood, respectively. In Tbx20 mutants, this divider does not form and results in deoxygenated blood flowing into the left atrium then is_associated_with::left ventricle, which ships the blood to the organs and muscles. Since deoxygenated blood should not be delivered to the tissues, the result is is_associated_with::cyanosis, or a bluish skin discoloration stemming from low oxygen concentration. Proper function of Tbx20 is essential because it controls other is_associated_with::genes that regulate is_associated_with::cardiomyocyte proliferation, such as Tbx2 and N-myc1. Cardiomyocytes are the basis for the correct architectural scheme of the heart, and if defects arise in these structures, proper heart development is likely unattainable.

Embryonic heart functions
Tbx20 is_associated_with::knockout mouse is_associated_with::embryos die at around or before E10.5 with is_associated_with::hypoplastic hearts. This gene has been implicated in coordinating cardiac proliferation, regional specification and formation of the cardiac chamber Congenital heart diseases involving TBX20 include defects in septation, chamber growth and valvulogenesis and increased Tbx20 expression was shown to cause congenital atrial septal defects, patent foramen ovale and cardiac valve defects.

Adult heart functions
In the fruitfly, knock-down of nmr (is_associated_with::neuromancer), is_associated_with::Drosophila's Tbx20 is_associated_with::homolog gene, led to slower heart rate, arrythmias and abnormal is_associated_with::myofibrillar architecture. Heterozygous Tbx20 knockout adult mice displayed is_associated_with::left ventricle dilation, decreased wall thickness and contractile abnormalities. is_associated_with::Homozygous conditional cardiomyocyte Tbx20 knockout adult mice died within 15 days after knockout induction. Mice hearts presented with dilated cardiomyopathy and contraction-related dysfunctions such as abnormal atrioventricular conduction, slower heart rate, altered ventricular is_associated_with::depolarization/repolarization and arrhythmias.

Known co-factors
Transcription factors is_associated_with::GATA4 and is_associated_with::NKX2-5 have been shown to physically interact with TBX20 and enhance gene expression.

Known downstream gene targets
Tbx2 was shown to be directly repressed by Tbx20 in the is_associated_with::myocardium. Analysis of data from is_associated_with::genome-wide is_associated_with::chromatin immunoprecipitation against TBX20 tagged with green is_associated_with::fluorescent protein in adult (6–8 weeks) mouse whole heart, coupled with analysis of genes differentially expressed upon loss of Tbx20, identified hundreds of putative TBX20 direct targets.