Targeted deletion of Hand2 in cardiac neural crest-derived cells influences cardiac gene expression and outflow tract development

Holler, Kristen L.; Hendershot, Tyler J.; Troy, Sophia E.; Vincentz, Joshua W.; Firulli, Anthony B.; Howard, Marthe J.

doi:10.1016/j.ydbio.2010.02.001

Cited by 59 publications

(64 citation statements)

References 132 publications

(212 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15 The Hand2 protein is involved in the development of the outflow tract and right ventricle. 16 Targeted deletion of miR-1 results in ventricular septal defects (VSDs). 15 The Irx5 protein regulates the expression of potassium channel genes like potassium voltagegated channel subfamily D member 2 (Kcnd2) and determines the cardiac ventricular repolarization gradient.…”

Section: Micrornas In Heart Developmentmentioning

confidence: 99%

MicroRNA in cardiovascular biology and disease

Wojciechowska¹,

Braniewska²,

2017

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are members of a non-coding RNA family. They act as negative regulators of protein translation by affecting messenger RNA (mRNA) stability; they modulate numerous signaling pathways and cellular processes, and are involved in cell-to-cell communication. Thus, studies on miRNAs offer an opportunity to improve our understanding of complex biological mechanisms. In the cardiovascular system, miRNAs control functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts. The pivotal role of miRNAs in the cardiovascular system provides a new perspective on the pathophysiology of disorders like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into circulation. Manipulation of miRNA activity may influence the course of a disease. Therefore, miRNAs have become an active field of research for developing new diagnostic and therapeutic tools. This review discusses emerging functions of miRNAs in cardiogenesis, heart regeneration and the pathophysiology of cardiovascular diseases.

show abstract

Section: Micrornas In Heart Developmentmentioning

confidence: 99%

MicroRNA in cardiovascular biology and disease

Wojciechowska¹,

Braniewska²,

2017

View full text Add to dashboard Cite

show abstract

“…Downregulated TFs with associated SOX9 peaks included Lef1, Pitx2 and Hand2. Loss of Lef1 (via TBX20 deletion), Pitx2 or Hand2 is associated with valve defects (Liu et al, 2002;Holler et al, 2010;Cai et al, 2013). TFs with the most reduced expression in Sox9 cKO valves were Twist1, Sox4 and Mecom.…”

Section: Sox9 Modulates the Transcript Levels Of Key Tfs In Heart Valmentioning

confidence: 99%

SOX9 modulates the expression of key transcription factors required for heart valve development

et al. 2015

View full text Add to dashboard Cite

Heart valve formation initiates when endothelial cells of the heart transform into mesenchyme and populate the cardiac cushions. The transcription factor SOX9 is highly expressed in the cardiac cushion mesenchyme, and is essential for heart valve development. Loss of Sox9 in mouse cardiac cushion mesenchyme alters cell proliferation, embryonic survival, and valve formation. Despite this important role, little is known about how SOX9 regulates heart valve formation or its transcriptional targets. Therefore, we mapped putative SOX9 binding sites by ChIP-Seq in E12.5 heart valves, a stage at which the valve mesenchyme is actively proliferating and initiating differentiation. Embryonic heart valves have been shown to express a high number of genes that are associated with chondrogenesis, including several extracellular matrix proteins and transcription factors that regulate chondrogenesis. Therefore, we compared regions of putative SOX9 DNA binding between E12.5 heart valves and E12.5 limb buds. We identified context-dependent and context-independent SOX9-interacting regions throughout the genome. Analysis of contextindependent SOX9 binding suggests an extensive role for SOX9 across tissues in regulating proliferation-associated genes including key components of the AP-1 complex. Integrative analysis of tissuespecific SOX9-interacting regions and gene expression profiles on Sox9-deficient heart valves demonstrated that SOX9 controls the expression of several transcription factors with previously identified roles in heart valve development, including Twist1, Sox4, Mecom and Pitx2. Together, our data identify SOX9-coordinated transcriptional hierarchies that control cell proliferation and differentiation during valve formation.

show abstract

“…ChIP using antibodies specific for native or tagged TFs, or specific histone modifications, followed by microarray analysis (ChIP-chip) or deep sequencing (ChIP-seq), is now commonly used. Mammalian cardiac TFs recently surveyed for target genes or effects on the transcriptome include MESP1, GATA4, MEF2A, NKX2-5, SRF, TBX3, TBX5, and TBX20 (Prall et al 2007;Holler et al 2010;Bondue et al 2011;He et al 2011;Schlesinger et al 2011;Shen et al 2011;Singh et al 2012). Furthermore, genome-wide binding profiles of the ubiquitously expressed histone acetyltransferases, p300 and CBP, cofactors of many transcriptional activators, have allowed the mapping of active and tissue-specific developmental enhancers without reference to specific TF binding (Blow et al 2010;May et al 2012).…”

Section: Genome-wide Technologymentioning

confidence: 99%

Genetic Networks Governing Heart Development

Waardenberg

Ramialison

Bouveret

et al. 2014

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

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-

show abstract

Targeted deletion of Hand2 in cardiac neural crest-derived cells influences cardiac gene expression and outflow tract development

Cited by 59 publications

References 132 publications

MicroRNA in cardiovascular biology and disease

MicroRNA in cardiovascular biology and disease

SOX9 modulates the expression of key transcription factors required for heart valve development

Genetic Networks Governing Heart Development

Contact Info

Product

Resources

About