Tbx5

Abstract

TBX5 is a member of the T-box transcription factor family and is primarily known for its role in cardiac and forelimb development. Human patients with dominant mutations in TBX5 are characterized by Holt–Oram syndrome, and show defects of the cardiac septa, cardiac conduction system, and the anterior forelimb. The range of cardiac defects associated with TBX5 mutations in humans suggests multiple roles for the transcription factor in cardiac development and function. Animal models demonstrate similar defects and have provided a useful platform for investigating the roles of TBX5 during embryonic development. During early cardiac development, TBX5 appears to act primarily as a transcriptional activator of genes associated with cardiomyocyte maturation and upstream of morphological signals for septation. During later cardiac development, TBX5 is required for patterning of the cardiac conduction system and maintenance of mature cardiomyocyte function. A comprehensive understanding of the integral roles of TBX5 throughout cardiac development and adult life will be critical for understanding human cardiac morphology and function.

Genetic Basis of Human Congenital Heart Disease

“…About 75% of cases of Holt-Oram syndrome are caused by mutations in TBX5, a member of the T-box family of transcription factors, which plays a role in regulation of gene expression during embryogenesis (Basson et al 1997;Li et al 1997c;McDermott et al 2005). TBX5 is expressed in the developing heart and limb and has been shown to be involved in the development of the cardiac septum and conduction system, consistent with the clinical findings in Holt-Oram syndrome (Steimle and Moskowitz 2017). Most of the variants in TBX5 are Kojuri et al 2007 (AR) aortic regurgitation, (AS) aortic stenosis, (ASD) atrial septal defect, (AVSD) atrioventricular septal defect, (BAV) bicuspid aortic valve, (CoA) coarctation of the aorta, (DORV) double outlet right ventricle, (HCM) hypertrophic cardiomyopathy, (HLHS) hypoplastic left heart syndrome, (MR) mitral regurgitation, (MVP) mitral valve prolapse, (PA) pulmonary atresia, (PDA) patent ductus arteriosus, (PFO) patent foramen ovale, (PS) pulmonary stenosis, (TA) truncus arteriosus, (TOF) tetralogy of Fallot, (TR) tricuspid regurgitation, (VSD) ventricular septal defect.…”

Incomplete Differentiation of Engrafted Bone Marrow Endothelial Progenitor Cells Initiates Hepatic Fibrosis in the Rat

“…Aberrant stem cell maturation has been described in developmental abnormalities, and cancer stem cells have been implicated in hematological and solid organ malignancies. The current study provides an example of incomplete maturation of adult stem cells in acquired, nonmalignant disease.…”

TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway

“…Knockout or knockdown analysis of Tbx5 in mice has revealed that the protein has a central role in cardiac development, probably through regulation of downstream genes, including Anf, Gata4, Nkx2. 5 and Brg1 [1,7,8].…”

“…TBX5 was identified as the gene responsible for Holt-Oram syndrome, a syndrome that is clinically characterized by radial ray deficiencies and cardiac defects, such as atrial septal defects (ASD) and ventricular septal defects (VSD). However, multiple variants in TBX5 have been associated with Holt-Oram syndrome, with variations in cardiac morphology and severity of the defect [1][2][3][4][5][6]. Knockout or knockdown analysis of Tbx5 in mice has revealed that the protein has a central role in cardiac development, probably through regulation of downstream genes, including Anf, Gata4, Nkx2.…”