scholarly journals Smyd1 Orchestrates Early Heart Development Through Positive and Negative Gene Regulation

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhen Wang ◽  
Robert J. Schwartz ◽  
Jing Liu ◽  
Fei Sun ◽  
Qi Li ◽  
...  
Keyword(s):  
Heart Development ◽  
Striated Muscle ◽  
Trichostatin A ◽  
Structural Defects ◽  
Reporter System ◽  
Cardiac Phenotype ◽  
Deacetylase Inhibitor ◽  
Heart Field ◽  
Polymerase Chain ◽  
Negative Gene

SET and MYND domain-containing protein 1 (Smyd1) is a striated muscle-specific histone methyltransferase. Our previous work demonstrated that deletion of Smyd1 in either cardiomyocytes or the outflow tract (OFT) resulted in embryonic lethality at E9.5, with cardiac structural defects such as truncation of the OFT and right ventricle and impaired expansion and proliferation of the second heart field (SHF). The cardiac phenotype was accompanied by the downregulation of ISL LIM Homeobox 1 (Isl1) and upregulation of atrial natriuretic factor (ANF). However, the mechanisms of Smyd1 regulating Isl1 and ANF during embryonic heart development remain to be elucidated. Here, we employed various biochemical and molecular biological approaches including chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR), pGL3 fluorescence reporter system, and co-immunoprecipitation (CoIP) and found that Smyd1 interacted with absent small homeotic-2-like protein (ASH2L) and activated the promoter of Isl1 by trimethylating H3K4. We also found that Smyd1 associated with HDAC to repress ANF expression using trichostatin A (TSA), a deacetylase inhibitor. In conclusion, Smyd1 participates in early heart development by upregulating the expression of Isl1 and downregulating the expression of ANF.

Overexpression of the tinman-related genes XNkx-2.5 and XNkx-2.3 in Xenopus embryos results in myocardial hyperplasia

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3549-3556 ◽  
Author(s):  
O.B. Cleaver ◽  
K.D. Patterson ◽  
P.A. Krieg
Keyword(s):  
Heart Development ◽  
Homeobox Gene ◽  
Cardiac Differentiation ◽  
Myocardial Cells ◽  
Differentiation Markers ◽  
Heart Field ◽  
Cardiac Mesoderm ◽  
Xenopus Laevis Embryos ◽  
Functional Homologues

Drosophila tinman is an NK-class homeobox gene required for formation of the dorsal vessel, the insect equivalent of the vertebrate heart. Vertebrate sequences related to tinman, such as mouse Nkx-2.5, chicken cNkx-2.5, Xenopus XNkx-2.5 and XNkx-2.3 are expressed in cardiac precursors and in tissues involved in induction of cardiac mesoderm. Mice which lack a functional Nkx-2.5 gene die due to cardiac defects. To determine the role of tinman-related sequences in heart development, we have overexpressed both XNkx-2.3 and XNkx-2.5 in Xenopus laevis embryos. The resulting embryos are morphologically normal except that they have enlarged hearts. The enlarged heart phenotype is due to a thickening of the myocardium caused by an increase in the overall number of myocardial cells (hyperplasia). Neither ectopic nor precocious expression of cardiac differentiation markers is detectable in overexpressing embryos. These results suggest that both XNkx-2.3 and XNkx-2.5 are functional homologues of tinman, responsible for maintenance of the heart field.

Abstract 257: Clonal Analysis Of Multipotent Cardiovascular Progenitors That Generate Cardiomyocytes During Development

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Konstantina Ioanna Sereti ◽  
Paniz Kamran Rashani ◽  
Peng Zhao ◽  
Reza Ardehali
Keyword(s):  
Single Cell ◽  
Heart Development ◽  
Cardiac Development ◽  
Clonal Analysis ◽  
Cardiac Cells ◽  
Single Cell Level ◽  
Reporter System ◽  
Cell Level ◽  
Cardiac Progenitors

It has been proposed that cardiac development in lower vertebrates is driven by the proliferation of cardiomyocytes. Similarly, cycling myocytes have been suggested to direct cardiac regeneration in neonatal mice after injury. Although, the role of cardiomyocyte proliferation in cardiac tissue generation during development has been well documented, the extent of this contribution as well as the role of other cell types, such as progenitor cells, still remains controversial. Here we used a novel stochastic four-color Cre-dependent reporter system (Rainbow) that allows labeling at a single cell level and retrospective analysis of the progeny. Cardiac progenitors expressing Mesp1 or Nkx2.5 were shown to be a source of cardiomyocytes during embryonic development while the onset of αMHC expression marked the developmental stage where the capacity of cardiac cells to proliferate diminishes significantly. Through direct clonal analysis we provide strong evidence supporting that cardiac progenitors, as opposed to mature cardiomyocytes, are the main source of cardiomyocytes during cardiac development. Moreover, we have identified quadri-, tri-, bi, and uni-potent progenitors that at a single cell level can generate cardiomyocytes, fibroblasts, endothelial and smooth muscle cells. Although existing cardiomyocytes undergo limited proliferation, our data indicates that it is mainly the progenitors that contribute to heart development. Furthermore, we show that the limited proliferation capacity of cardiomyocytes observed during normal development was enhanced following neonatal cardiac injury allowing almost complete regeneration of the scared tissue. However, this ability was largely absent in adult injured hearts. Detailed characterization of dividing cardiomyocytes and proliferating progenitors would greatly benefit the development of novel therapeutic options for cardiovascular diseases.

scholarly journals Androgenesis-Based Doubled Haploidy: Past, Present, and Future Perspectives

2022 ◽  
Vol 12 ◽  
Author(s):  
Brett Hale ◽  
Alison M. R. Ferrie ◽  
Sreekala Chellamma ◽  
J. Pon Samuel ◽  
Gregory C. Phillips
Keyword(s):  
Cell Fate ◽  
Trichostatin A ◽  
Crop Improvement ◽  
Past Research ◽  
Culture Optimization ◽  
Protocol Development ◽  
Doubled Haploidy ◽  
Deacetylase Inhibitor ◽  
Cycle Regulation ◽  
External Stimuli

Androgenesis, which entails cell fate redirection within the microgametophyte, is employed widely for genetic gain in plant breeding programs. Moreover, androgenesis-responsive species provide tractable systems for studying cell cycle regulation, meiotic recombination, and apozygotic embryogenesis within plant cells. Past research on androgenesis has focused on protocol development with emphasis on temperature pretreatments of donor plants or floral buds, and tissue culture optimization because androgenesis has different nutritional requirements than somatic embryogenesis. Protocol development for new species and genotypes within responsive species continues to the present day, but slowly. There is more focus presently on understanding how protocols work in order to extend them to additional genotypes and species. Transcriptomic and epigenetic analyses of induced microspores have revealed some of the cellular and molecular responses required for or associated with androgenesis. For example, microRNAs appear to regulate early microspore responses to external stimuli; trichostatin-A, a histone deacetylase inhibitor, acts as an epigenetic additive; ά-phytosulfokine, a five amino acid sulfated peptide, promotes androgenesis in some species. Additionally, present work on gene transfer and genome editing in microspores suggest that future endeavors will likely incorporate greater precision with the genetic composition of microspores used in doubled haploid breeding, thus likely to realize a greater impact on crop improvement. In this review, we evaluate basic breeding applications of androgenesis, explore the utility of genomics and gene editing technologies for protocol development, and provide considerations to overcome genotype specificity and morphogenic recalcitrance in non-model plant systems.

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.

scholarly journals Temporally Distinct Six2 -Positive Second Heart Field Progenitors Regulate Mammalian Heart Development and Disease

Cell Reports ◽  
2017 ◽  
Vol 18 (4) ◽  
pp. 1019-1032 ◽  
Author(s):  
Zhengfang Zhou ◽  
Jingying Wang ◽  
Chaoshe Guo ◽  
Weiting Chang ◽  
Jian Zhuang ◽  
...  
Keyword(s):  
Heart Development ◽  
Second Heart Field ◽  
Mammalian Heart ◽  
Heart Field
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