GATA factors in vertebrate heart development and disease

2006 ◽  
Vol 8 (22) ◽  
pp. 1-20 ◽  
Author(s):  
Alison Brewer ◽  
John Pizzey
Keyword(s):  
Transcription Factors ◽  
Heart Development ◽  
Regulatory Networks ◽  
Cardiac Development ◽  
Cellular Mechanisms ◽  
Cardiac Morphogenesis ◽  
Functional Roles ◽  
Gata Factors ◽  
Evolutionarily Conserved ◽  
Heart Formation

Vertebrate heart formation is dependent upon complex hierarchical gene regulatory networks, which effect both the specification and differentiation of cardiomyocytes and subsequently cardiac morphogenesis. GATA-4, -5 and -6 comprise an evolutionarily conserved subfamily of transcription factors, which are expressed within the precardiac mesoderm from early stages in its specification and continue to be expressed within the adult heart. We review here the functional roles of individual GATA transcription factors in cardiac development, normal homeostasis and disease. We also review the cellular mechanisms employed to regulate the expression and downstream targets of the different GATA factors.

microRNAs in cardiac development and regeneration

2013 ◽  
Vol 125 (4) ◽  
pp. 151-166 ◽  
Author(s):  
Enzo R. Porrello
Keyword(s):  
Gene Expression ◽  
Heart Development ◽  
Regulatory Networks ◽  
Cardiac Development ◽  
Regulation Of Gene Expression ◽  
Cardiac Regeneration ◽  
Cardiac Differentiation ◽  
Evolutionarily Conserved ◽  
Post Transcriptional Regulation ◽  
Therapeutic Possibilities

Heart development involves the precise orchestration of gene expression during cardiac differentiation and morphogenesis by evolutionarily conserved regulatory networks. miRNAs (microRNAs) play important roles in the post-transcriptional regulation of gene expression, and recent studies have established critical functions for these tiny RNAs in almost every facet of cardiac development and disease. The realization that miRNAs are amenable to therapeutic manipulation has also generated considerable interest in the potential of miRNA-based drugs for the treatment of a number of human diseases, including cardiovascular disease. In the present review, I discuss well-established and emerging roles of miRNAs in cardiac development, their relevance to congenital heart disease and unresolved questions in the field for future investigation, as well as emerging therapeutic possibilities for cardiac regeneration.

scholarly journals Lamb1a regulates atrial growth by limiting excessive, contractility-dependent second heart field addition during zebrafish heart development

2021 ◽  
Author(s):  
Christopher J. Derrick ◽  
Eric J. G. Pollitt ◽  
Ashley Sanchez Sevilla Uruchurtu ◽  
Farah Hussein ◽  
Emily S. Noёl
Keyword(s):  
Heart Development ◽  
Cardiac Development ◽  
Basement Membranes ◽  
Atrioventricular Canal ◽  
Cardiac Morphogenesis ◽  
Heart Morphogenesis ◽  
Second Heart Field ◽  
Heart Field ◽  
Heart Size ◽  
Zebrafish Heart

AbstractDuring early vertebrate heart development, the heart transitions from a linear tube to a complex asymmetric structure. This process includes looping of the tube and ballooning of the emerging cardiac chambers, which occur simultaneously with growth of the heart. A key driver of cardiac growth is deployment of cells from the Second Heart Field (SHF) into both poles of the heart, with cardiac morphogenesis and growth intimately linked in heart development. Laminin is a core component of extracellular matrix (ECM) basement membranes, and although mutations in specific laminin subunits are linked with a variety of cardiac abnormalities, including congenital heart disease and dilated cardiomyopathy, no role for laminin has been identified in early vertebrate heart morphogenesis. We identified dynamic, tissue-specific expression of laminin subunit genes in the developing zebrafish heart, supporting a role for laminins in heart morphogenesis.lamb1amutants exhibit cardiomegaly from 2dpf onwards, with subsequent progressive defects in cardiac morphogenesis characterised by a failure of the chambers to compact around the developing atrioventricular canal. We show that loss oflamb1aresults in excess addition of SHF cells to the atrium, revealing that Lamb1a functions to limit heart size during cardiac development by restricting SHF addition to the venous pole.lamb1amutants exhibit hallmarks of altered haemodynamics, and specifically blocking cardiac contractility inlamb1amutants rescues heart size and atrial SHF addition. Furthermore, we identify that FGF and RA signalling, two conserved pathways promoting SHF addition, are regulated by heart contractility and are dysregulated inlamb1amutants, suggesting that laminin mediates interactions between SHF deployment, heart biomechanics, and biochemical signalling during heart development. Together, this describes the first requirement for laminins in early vertebrate heart morphogenesis, reinforcing the importance of specialised ECM composition in cardiac development.

Regulation of the ANF and BNP promoters by GATA factors: Lessons learned for cardiac transcription

2001 ◽  
Vol 79 (8) ◽  
pp. 673-681 ◽  
Author(s):  
Kevin McBride ◽  
Mona Nemer
Keyword(s):  
Transcription Factors ◽  
Natriuretic Peptide ◽  
Regulatory Networks ◽  
Current Knowledge ◽  
Lessons Learned ◽  
Clinical Markers ◽  
Gata Factors ◽  
Major Mechanism ◽  
Genes Encoding ◽  
Cardiac Gene

The identification and molecular cloning of the cardiac transcription factors GATA-4, -5, and -6 has greatly contributed to our understanding of how tissue-specific transcription is achieved during cardiac growth and development. Through analysis of their interacting partners, it has also become apparent that a major mechanism underlying spatial and temporal specificity within the heart as well as in the response to cardiogenic regulators is the combinatorial interaction between cardiac-restricted and inducible transcription factors. The cardiac GATA factors appear to be fundamental contributors to these regulatory networks. Two of the first targets identified for the cardiac GATA factors were the natriuretic peptide genes encoding atrial natriuretic factor (ANF) and B-type natriuretic peptide (BNP), the major heart secretory products that are also accepted clinical markers of the diseased heart. Studies using the ANF and BNP promoters as models of cardiac-specific transcription have unraveled the pivotal role that GATA proteins play in cardiac gene expression. We review the current knowledge on the modulation of the natriuretic peptide promoters by GATA factors, including examples of combinatorial interactions between GATA proteins and diverse transcription factors.Key words: ANF, BNP, GATA factors, cardiac transcription.

scholarly journals TBX5 drives Aldh1a2 expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development

2021 ◽  
Author(s):  
Scott A rankin ◽  
Jeffery D Steimle ◽  
Xinan Yang ◽  
Ariel B Rydeen ◽  
Kunal Agarwal ◽  
...  
Keyword(s):  
Heart Development ◽  
Regulatory Networks ◽  
Lateral Plate ◽  
T Box ◽  
Terrestrial Vertebrates ◽  
Regulatory Module ◽  
Evolutionarily Conserved ◽  
Terrestrial Life ◽  
Gene Regulatory ◽  
Foregut Endoderm

The gene regulatory networks that coordinate the development of the cardiac and pulmonary systems are essential for terrestrial life but poorly understood. The T-box transcription factor Tbx5 is critical for both pulmonary specification and heart development, but how these activities are mechanistically integrated remains unclear. We show that Tbx5 regulates an evolutionarily conserved retinoic acid (RA)-Hedgehog-Wnt signaling cascade coordinating cardiopulmonary development. We demonstrate that Tbx5 directly maintains expression of the RA-synthesizing enzyme Aldh1a2 in the foregut lateral plate mesoderm via an intronic enhancer that is evolutionarily conserved among terrestrial vertebrates. Tbx5 promotes posterior second heart field identity in a positive feedback loop with RA, antagonizing a Fgf8-Cyp regulatory module and restricting FGF activity to the anterior. Tbx5/Aldh1a2-dependent RA signaling also directly activates Shh transcription in the adjacent foregut endoderm through the conserved MACS1 enhancer. Epithelial Hedgehog then signals back to the mesoderm, where together with Tbx5 it activates expression of Wnt2/2b that ultimately induce pulmonary fate in the foregut endoderm. These results provide mechanistic insight into the interrelationship between heart and lung development informing cardiopulmonary evolution and birth defects.

scholarly journals Role of GATA factors in development, differentiation, and homeostasis of the small intestinal epithelium

2014 ◽  
Vol 306 (6) ◽  
pp. G474-G490 ◽  
Author(s):  
Boaz E. Aronson ◽  
Kelly A. Stapleton ◽  
Stephen D. Krasinski
Keyword(s):  
Transcription Factors ◽  
Intestinal Epithelium ◽  
Regulatory Networks ◽  
Small Intestinal Epithelium ◽  
Gata Factors ◽  
Evolution And Development ◽  
Multiple Context ◽  
Small Intestinal ◽  
Context Specific

The small intestinal epithelium develops from embryonic endoderm into a highly specialized layer of cells perfectly suited for the digestion and absorption of nutrients. The development, differentiation, and regeneration of the small intestinal epithelium require complex gene regulatory networks involving multiple context-specific transcription factors. The evolutionarily conserved GATA family of transcription factors, well known for its role in hematopoiesis, is essential for the development of endoderm during embryogenesis and the renewal of the differentiated epithelium in the mature gut. We review the role of GATA factors in the evolution and development of endoderm and summarize our current understanding of the function of GATA factors in the mature small intestine. We offer perspective on the application of epigenetics approaches to define the mechanisms underlying context-specific GATA gene regulation during intestinal development.

scholarly journals Phosphodiesterases Expression during Murine Cardiac Development

2021 ◽  
Vol 22 (5) ◽  
pp. 2593
Author(s):  
Thays Maria da Conceição Silva Carvalho ◽  
Silvia Cardarelli ◽  
Mauro Giorgi ◽  
Andrea Lenzi ◽  
Andrea M. Isidori ◽  
...  
Keyword(s):  
Heart Development ◽  
Fetal Heart ◽  
Cardiac Development ◽  
Large Family ◽  
Hydrolytic Activity ◽  
Development Data ◽  
Heart Formation ◽  
Camp And Cgmp ◽  
Developing Mice

3′-5′ cyclic nucleotide phosphodiesterases (PDEs) are a large family of enzymes playing a fundamental role in the control of intracellular levels of cAMP and cGMP. Emerging evidence suggested an important role of phosphodiesterases in heart formation, but little is known about the expression of phosphodiesterases during cardiac development. In the present study, the pattern of expression and enzymatic activity of phosphodiesterases was investigated at different stages of heart formation. C57BL/6 mice were mated and embryos were collected from 14.5 to 18.5 days of development. Data obtained by qRT-PCR and Western blot analysis showed that seven different isoforms are expressed during heart development, and PDE1C, PDE2A, PDE4D, PDE5A and PDE8A are modulated from E14.5 to E18.5. In heart homogenates, the total cAMP and cGMP hydrolytic activity is constant at the evaluated times, and PDE4 accounts for the majority of the cAMP hydrolyzing ability and PDE2A accounts for cGMP hydrolysis. This study showed that a subset of PDEs is expressed in developing mice heart and some of them are modulated to maintain constant nucleotide phosphodiesterase activity in embryonic and fetal heart.

scholarly journals Building and Repairing the Heart: What Can We Learn from Embryonic Development?

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ana G. Freire ◽  
Tatiana P. Resende ◽  
Perpétua Pinto-do-Ó
Keyword(s):  
Heart Development ◽  
Cardiac Development ◽  
Embryonic Stem ◽  
Cardiac Pathophysiology ◽  
Distinct Cell ◽  
Cell Sources ◽  
Cardiac Lineage ◽  
Heart Formation ◽  
Tissue Recovery

Mammalian heart formation is a complex morphogenetic event that depends on the correct temporal and spatial contribution of distinct cell sources. During cardiac formation, cellular specification, differentiation, and rearrangement are tightly regulated by an intricate signaling network. Over the last years, many aspects of this network have been uncovered not only due to advances in cardiac development comprehension but also due to the use of embryonic stem cells (ESCs)in vitromodel system. Additionally, several of these pathways have been shown to be functional or reactivated in the setting of cardiac disease. Knowledge withdrawn from studying heart development, ESCs differentiation, and cardiac pathophysiology may be helpful to envisage new strategies for improved cardiac repair/regeneration. In this review, we provide a comparative synopsis of the major signaling pathways required for cardiac lineage commitment in the embryo and murine ESCs. The involvement and possible reactivation of these pathways following heart injury and their role in tissue recovery will also be discussed.

scholarly journals GATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate

2020 ◽  
Author(s):  
Mengyi Song ◽  
Xuefei Yuan ◽  
Claudia Racioppi ◽  
Meaghan Leslie ◽  
Anastasiia Aleksandrova ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Heart Development ◽  
Gene Expression Analysis ◽  
Cell Fate Decisions ◽  
Evolutionarily Conserved ◽  
Cell Gene Expression ◽  
Cell Gene ◽  
Cardiac Mesoderm ◽  
Invertebrate Chordate

AbstractGATA4/5/6 transcription factors play essential, conserved roles in heart development. How these factors mediate the transition from multipotent mesoderm progenitors to a committed cardiac fate is unclear. To understand how GATA4/5/6 modulate cell fate decisions we labelled, isolated, and performed single-cell gene expression analysis on cells that express gata5 at pre-cardiac time points spanning gastrulation to somitogenesis. We found that most mesendoderm-derived lineages had dynamic gata5/6 expression. In the absence of Gata5/6, the population structure of mesendoderm-derived cells was dramatically altered. In addition to the expected absence of cardiac mesoderm, we observed a concomitant expansion of cranial-pharyngeal mesoderm. Functional genetic analyses in zebrafish and the invertebrate chordate Ciona, which possess a single GATA4/5/6 homolog, revealed an essential and cell-autonomous role for GATA4/5/6 in promoting cardiac and inhibiting pharyngeal mesoderm identity. Overall, the maintenance and repression of GATA4/5/6 activity plays a critical, evolutionarily conserved role in early development.

scholarly journals miR-128a Acts as a Regulator in Cardiac Development by Modulating Differentiation of Cardiac Progenitor Cell Populations

2020 ◽  
Vol 21 (3) ◽  
pp. 1158 ◽  
Author(s):  
Sarah C. Hoelscher ◽  
Theresia Stich ◽  
Anne Diehm ◽  
Harald Lahm ◽  
Martina Dreßen ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Heart Development ◽  
Regulatory Networks ◽  
Progenitor Cell ◽  
Cardiac Development ◽  
Loss Of Function ◽  
And Function ◽  
Cardiac Transcription Factors ◽  
Beating Frequency

MicroRNAs (miRs) appear to be major, yet poorly understood players in regulatory networks guiding cardiogenesis. We sought to identify miRs with unknown functions during cardiogenesis analyzing the miR-profile of multipotent Nkx2.5 enhancer cardiac progenitor cells (NkxCE-CPCs). Besides well-known candidates such as miR-1, we found about 40 miRs that were highly enriched in NkxCE-CPCs, four of which were chosen for further analysis. Knockdown in zebrafish revealed that only miR-128a affected cardiac development and function robustly. For a detailed analysis, loss-of-function and gain-of-function experiments were performed during in vitro differentiations of transgenic murine pluripotent stem cells. MiR-128a knockdown (1) increased Isl1, Sfrp5, and Hcn4 (cardiac transcription factors) but reduced Irx4 at the onset of cardiogenesis, (2) upregulated Isl1-positive CPCs, whereas NkxCE-positive CPCs were downregulated, and (3) increased the expression of the ventricular cardiomyocyte marker Myl2 accompanied by a reduced beating frequency of early cardiomyocytes. Overexpression of miR-128a (4) diminished the expression of Isl1, Sfrp5, Nkx2.5, and Mef2c, but increased Irx4, (5) enhanced NkxCE-positive CPCs, and (6) favored nodal-like cardiomyocytes (Tnnt2+, Myh6+, Shox2+) accompanied by increased beating frequencies. In summary, we demonstrated that miR-128a plays a so-far unknown role in early heart development by affecting the timing of CPC differentiation into various cardiomyocyte subtypes.

scholarly journals Ageing, TOR and amino acid restriction: a cross-tissue transcriptional network connects GATA factors to Drosophila longevity

2016 ◽  
Author(s):  
Adam J Dobson ◽  
Xiaoli He ◽  
Eric Blanc ◽  
Ekin Bolukbasi ◽  
Yodit Feseha ◽  
...  
Keyword(s):  
Amino Acids ◽  
Transcription Factors ◽  
Amino Acid ◽  
Early Life ◽  
Transcriptional Regulators ◽  
Essential Amino Acids ◽  
Tissue Specific ◽  
Gata Factors ◽  
Transcriptional Reprogramming ◽  
Evolutionarily Conserved

AbstractAnimal lifespan can be extended by dietary restriction (DR), but at a cost to fitness. This phenomenon depends on essential amino acids (EAAs) and TOR signalling, but roles of specific tissues and downstream transcriptional regulators are poorly characterised. Manipulating relevant transcription factors (TFs) specifically in lifespan-limiting tissues may ameliorate ageing without costs of DR. Here we identify TFs which regulate the DR phenotype in Drosophila, analysing organs as an interacting system and reducing its transcriptional complexity by two orders of magnitude. Evolutionarily conserved GATA TFs are predicted to regulate the overlapping effects of DR and TOR on organs, and genetic analyses confirmed that these TFs interact with diet to determine lifespan. Importantly, Srp knockdown insulated fly lifespan from the pernicious effects of EAAs, but tissue-specific knockdown reduced the corrolary costs. These results provide the first indication that benefits of EAAs for early-life fitness can be decoupled from longevity by tissue-specific transcriptional reprogramming.

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