scholarly journals Krüppel-like factor gene function in the ctenophore Mnemiopsis leidyi assessed by CRISPR/Cas9-mediated genome editing

Development ◽  
2021 ◽  
Author(s):  
Jason S. Presnell ◽  
William E. Browne
Keyword(s):  
Cell Proliferation ◽  
Transcription Factors ◽  
Genome Editing ◽  
Gene Function ◽  
Cell Types ◽  
Abnormal Development ◽  
Mnemiopsis Leidyi ◽  
Animal Evolution ◽  
Animal Development

The Krüppel-like factor (Klf) gene family encodes for transcription factors that play an important role in the regulation of stem cell proliferation, cell differentiation, and development in bilaterians. While Klf genes have been shown to functionally specify various cell types in non-bilaterian animals, their role in early diverging animal lineages has not been assessed. Thus, the ancestral activity of these transcription factors in animal development is not well understood. The ctenophore Mnemiopsis leidyi has emerged as an important non-bilaterian model system for understanding early animal evolution. Here we characterize the expression and functional role of Klf genes during M. leidyi embryogenesis. Zygotic Klf gene function was assessed with both CRISPR/Cas9-mediated genome editing and splice-blocking morpholino oligonucleotide knockdown approaches. Abrogation of zygotic Klf expression during M. leidyi embryogenesis results in abnormal development of several organs including the pharynx, tentacle bulbs, and apical organ. Our data suggest an ancient role for Klf genes in regulating endodermal patterning, possibly through regulation of cell proliferation.

scholarly journals Krüppel-like factor gene function in the ctenophore Mnemiopsis leidyi assessed by CRISPR/Cas9-mediated genome editing

2019 ◽  
Author(s):  
Jason S Presnell ◽  
William E Browne
Keyword(s):  
Transcription Factors ◽  
Genome Editing ◽  
Gene Function ◽  
Functional Role ◽  
Cell Types ◽  
Mnemiopsis Leidyi ◽  
Morpholino Oligonucleotide ◽  
Animal Evolution ◽  
Animal Development ◽  
Summary Statement

AbstractThe Krüppel-like factor (Klf) gene family encodes for transcription factors that play an important role in the regulation of stem cell proliferation, cell differentiation, and development in bilaterians. While Klf genes have been shown to be expressed in various cell types in non-bilaterian animals, their functional role in early diverging animal lineages has not been assessed. Thus, the ancestral activity of these transcription factors in animal development is not well understood. The ctenophore Mnemiopsis leidyi has emerged as an important non-bilaterian model system for understanding early animal evolution. Here we characterize the expression and functional role of Klf genes during M. leidyi embryogenesis. Zygotic Klf gene function was assessed with both CRISPR/Cas9-mediated genome editing knockout and splice-blocking morpholino oligonucleotide knockdown approaches. Abrogation of zygotic Klf expression during M. leidyi embryogenesis results in the irregular development of several organs including the pharynx, tentacle bulbs, and apical organ. Our data suggest an ancient role for Klf genes in regulating endodermal patterning.Summary StatementUsing morpholino oligonucleotide knockdown and CRISPR/Cas9 genome editing, this study shows that in the ctenophore Mnemiopsis leidyi, tissues derived from the endoderm are dependent upon Klf5 ortholog expression for proper development and patterning.

The paracaspase MALT1 in psoriasis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Stephan Hailfinger ◽  
Klaus Schulze-Osthoff
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Transcription Factors ◽  
Skin Disease ◽  
Cell Types ◽  
Cytokine Receptors ◽  
Molecular Scaffold ◽  
Therapeutic Implications ◽  
Stimulation Of

Abstract Psoriasis is a frequent autoimmune-related skin disease, which involves various cell types such as T cells, keratinocytes and dendritic cells. Genetic variations, such as mutations of CARD14, can promote the development of the disease. CARD14 mutations as well as the stimulation of immune and cytokine receptors activate the paracaspase MALT1, a potent activator of the transcription factors NF-κB and AP-1. The disease-promoting role of MALT1 for psoriasis is mediated by both its protease activity as well as its molecular scaffold function. Here, we review the importance of MALT1-mediated signaling and its therapeutic implications in psoriasis.

Regulation of Pax-3 expression in the dermomyotome and its role in muscle development

Development ◽  
1994 ◽  
Vol 120 (4) ◽  
pp. 957-971 ◽  
Author(s):  
M. Goulding ◽  
A. Lumsden ◽  
A.J. Paquette
Keyword(s):  
Transcription Factors ◽  
Muscle Development ◽  
Cell Types ◽  
Axial Skeleton ◽  
Mouse Embryos ◽  
Related Gene ◽  
Paired Domain ◽  
Trunk Musculature ◽  
Somitic Mesoderm

The segmented mesoderm in vertebrates gives rise to a variety of cell types in the embryo including the axial skeleton and muscle. A number of transcription factors containing a paired domain (Pax proteins) are expressed in the segmented mesoderm during embryogenesis. These include Pax-3 and a closely related gene, Pax-7, both of which are expressed in the segmental plate and in the dermomyotome. In this paper, we show that signals from the notochord pattern the expression of Pax-3, Pax-7 and Pax-9 in somites and the subsequent differentiation of cell types that arise from the somitic mesoderm. We directly assess the role of the Pax-3 gene in the differentiation of cell types derived from the dermomyotome by analyzing the development of muscle in splotch mouse embryos which lack a functional Pax-3 gene. A population of Pax-3-expressing cells derived from the dermomyotome that normally migrate into the limb are absent in homozygous splotch embryos and, as a result, limb muscles are lost. No abnormalities were detected in the trunk musculature of splotch embryos indicating that Pax-3 is necessary for the development of the limb but not trunk muscle.

scholarly journals Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Bhaskar Ponugoti ◽  
Guangyu Dong ◽  
Dana T. Graves
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cellular Response ◽  
Cell Damage ◽  
Cell Types ◽  
Biological Processes ◽  
Oxygen Species ◽  
Forkhead Transcription Factors ◽  
Foxo Transcription Factors

Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS) and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 transcription factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO transcription factors in mediating oxidative stress-induced cellular response.

scholarly journals Proto-oncogenes of the fos/jun family of transcription factors are positive regulators of myeloid differentiation.

1993 ◽  
Vol 13 (2) ◽  
pp. 841-851 ◽  
Author(s):  
K A Lord ◽  
A Abdollahi ◽  
B Hoffman-Liebermann ◽  
D A Liebermann
Keyword(s):  
Transcription Factors ◽  
Leucine Zipper ◽  
Culture Media ◽  
Terminal Differentiation ◽  
Cell Types ◽  
Primary Response ◽  
Myeloid Differentiation ◽  
Active Transcription

The proto-oncogenes c-jun, junB, junD, and c-fos recently have been shown to encode for transcription factors with a leucine zipper that mediates dimerization to constitute active transcription factors; juns were shown to dimerize with each other and with c-fos, whereas fos was shown to dimerize only with juns. After birth, hematopoietic cells of the myeloid lineage, and some other terminally differentiated cell types, express high levels of c-fos. Still, the role of fos/jun transcription factors in normal myelopoiesis or in leukemogenesis has not been established. Recently, c-jun, junB, and junD were identified as myeloid differentiation primary response genes stably expressed following induction of terminal differentiation of myeloblastic leukemia M1 cells. Intriguingly, c-fos, though induced during normal myelopoiesis, was not induced upon M1 differentiation. To gain further insights into the role of fos/jun in normal myelopoiesis and leukemogenicity, M1fos and M1junB cell lines, which constitutively express c-fos and junB, respectively, were established. It was shown that enforced expression of c-fos, and to a lesser extent junB, in M1 cells results in both an increased propensity to differentiate and a reduction in the aggressiveness of the M1 leukemic phenotype. M1fos cells constitutively expressed immediate-early and late genetic markers of differentiated M1 cells. The in vitro differentiation of normal myeloblasts into mature macrophages and granulocytes, as well as the increased propensity of M1fos leukemic myeloblasts to be induced for terminal differentiation, was dramatically impaired with use of c-fos antisense oligomers in the culture media. Taken together, these observations show that the proto-oncogenes which encode for fos/jun transcription factors play important roles in promoting myeloid differentiation. The ability of the M1 leukemic myeloblasts to be induced for terminal differentiation in the absence of apparent fos expression indicates that there is some redundancy among the fos/jun family of transcription factors in promoting myeloid differentiation; however, juns alone cannot completely compensate for the lack of fos. Thus, genetic lesions affecting fos/jun expression may play a role in the development of "preleukemic" myelodysplastic syndromes and their further progression to leukemias.

scholarly journals Role Of WOX And KNOX Transcription Factors In Plant Development And Tumor Formation

2006 ◽  
Vol 4 (4) ◽  
pp. 3-9
Author(s):  
Maria A Osipova ◽  
Elena A Dolgikh ◽  
Ludmila A Lutova
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Plant Development ◽  
Plant Hormones ◽  
Tumor Formation ◽  
Animal Tumor ◽  
The Common ◽  
Meristem Maintenance

Homeodomain-containing transcription factors are the important regulators of multicellular organism's development. Plant transcription factors WOX and KNOX play the key role in meristem maintenance, controlling cell proliferation and preventing differentiation. The precise mechanism of WOX and KNOX action hasn't been well studied, however these transcription factors were shown to play the important role in plant hormones homeostasis, cytokinins in particular. Plant transcription factors of KNOX group demonstrate the similarities in structure and are supposed have the common origin with animal transcription factors of MEIS group. This review describes WOX and KNOX transcription factor families, their interaction with plant hormones. The role of homeodomain-containing transcription factors in plant and animal tumor formation is discussed.

scholarly journals Regulation of IRE1α by the small molecule inhibitor 4μ8c in hepatoma cells

2017 ◽  
Vol 4 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Claire Stewart ◽  
Andrea Estrada ◽  
Paul Kim ◽  
Dong Wang ◽  
Yuren Wei ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Small Molecule ◽  
Pancreatic Beta Cells ◽  
Cell Types ◽  
Small Molecule Inhibitor ◽  
Hepatoma Cells ◽  
Rnase Activity ◽  
Molecule Inhibitor ◽  
Target Effects

AbstractThe unfolded protein response (UPR) is activated in response to impairments of the folding environment in the endoplasmic reticulum (ER). The most conserved arm of the UPR, inositol-requiring ER-to-nucleus signaling protein (IRE1α), has been linked to the regulation of a diverse array of cellular processes including ER-associated degradation, inflammatory signaling, cell proliferation and membrane biogenesis. Recent studies have utilized the selective, small molecule inhibitor, 4μ8c, to examine the role of IRE1α endoribonuclease (RNase) activity in various cell types including multiple myeloma, mouse embryonic fibroblasts and pancreatic beta cells [1-5]. In the present study we utilized this inhibitor to examine the role of IRE1α RNase activity in hepatoma cells (H4IIE), specifically concentrating on cell proliferation and the identification of potential off target effects under both unstressed and stressed conditions. Experiments were performed in H4IIE hepatoma cells in the absence (control conditions (LG)) or presence (LG + Thapsigargin (Thap)) of ER stress. The presence of 4μ8c decreased IRE1α RNase activity, based on reduced splicing of X-box binding protein-1 (XBP1s) and regulated IRE1α-dependent decay of mRNA in both treatments and at concentrations ranging from 10-90 μM. Cell proliferation was significantly reduced at higher concentrations (> 60 μM 4μ8c) in unstressed cells and displayed a dose-response relationship with 4μ8c in both treatments. The presence of 4μ8c did not promote cytoxicity in either of the treatment conditions but higher concentrations of the inhibitor (60 μM) were associated with apparent off-target or compensatory responses that were not observed at 10 μM. Overall, the small-molecule inhibitor, 4μ8c is an effective inhibitor of IRE1α RNase activity in H4IIE cells. Potential off-target effects associated with this inhibitor require the use of multiple inhibitor concentrations in all experiments.

scholarly journals Biological Effects of Mammalian Translationally Controlled Tumor Protein (TCTP) on Cell Death, Proliferation, and Tumorigenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Michiyo Nagano-Ito ◽  
Shinichi Ichikawa
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Immune Responses ◽  
Biological Effects ◽  
Cell Types ◽  
Multifunctional Protein ◽  
Antiapoptotic Protein ◽  
Translationally Controlled Tumor Protein ◽  
Antiapoptotic Activity

Translationally controlled tumor protein (TCTP) is a highly conserved protein found in eukaryotes, across animal and plant kingdoms and even in yeast. Mammalian TCTP is ubiquitously expressed in various tissues and cell types. TCTP is a multifunctional protein which plays important roles in a number of cell physiological events, such as immune responses, cell proliferation, tumorigenicity, and cell death, including apoptosis. Recent identification of TCTP as an antiapoptotic protein has attracted interest of many researchers in the field. The mechanism of antiapoptotic activity, however, has not been solved completely, and TCTP might inhibit other types of cell death. Cell death (including apoptosis) is closely linked to proliferation and tumorigenesis. In this context, we review recent findings regarding the role of TCTP in cell death, proliferation, and tumorigenesis and discuss the mechanisms.

scholarly journals Corticosteroid receptors, macrophages and cardiovascular disease

2009 ◽  
Vol 42 (6) ◽  
pp. 449-459 ◽  
Author(s):  
Amanda J Rickard ◽  
Morag J Young
Keyword(s):  
Cardiovascular Disease ◽  
Transcription Factors ◽  
Glucocorticoid Receptor ◽  
Mineralocorticoid Receptor ◽  
Cell Types ◽  
Current Understanding ◽  
Corticosteroid Receptors ◽  
Monocytes And Macrophages ◽  
Anti Inflammatory

The mineralocorticoid receptor (MR) and glucocorticoid receptor are ligand-activated transcription factors that have important physiological and pathophysiological actions in a broad range of cell types including monocytes and macrophages. While the glucocorticoids cortisol and corticosterone have well-described anti-inflammatory actions on both recruited and tissue resident macrophages, a role for the mineralocorticoid aldosterone in these cells is largely undefined. Emerging evidence, however, suggests that MR signalling may promote pro-inflammatory effects. This review will discuss the current understanding of the role of corticosteroid receptors in macrophages and their effect on diseases involving inflammation, with a particular focus on cardiovascular disease.

scholarly journals Whole-organism cellular gene-expression atlas reveals conserved cell types in the ventral nerve cord of Platynereis dumerilii

2017 ◽  
Vol 114 (23) ◽  
pp. 5878-5885 ◽  
Author(s):  
Hernando Martínez Vergara ◽  
Paola Yanina Bertucci ◽  
Peter Hantz ◽  
Maria Antonietta Tosches ◽  
Kaia Achim ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Cell Types ◽  
Animal Evolution ◽  
Mapping Algorithm ◽  
Differentiated Cells ◽  
Rich Diversity ◽  
Platynereis Dumerilii ◽  
Expression Atlas

The comparative study of cell types is a powerful approach toward deciphering animal evolution. To avoid selection biases, however, comparisons ideally involve all cell types present in a multicellular organism. Here, we use image registration and a newly developed “Profiling by Signal Probability Mapping” algorithm to generate a cellular resolution 3D expression atlas for an entire animal. We investigate three-segmented young worms of the marine annelid Platynereis dumerilii, with a rich diversity of differentiated cells present in relatively low number. Starting from whole-mount expression images for close to 100 neural specification and differentiation genes, our atlas identifies and molecularly characterizes 605 bilateral pairs of neurons at specific locations in the ventral nerve cord. Among these pairs, we identify sets of neurons expressing similar combinations of transcription factors, located at spatially coherent anterior-posterior, dorsal-ventral, and medial-lateral coordinates that we interpret as cell types. Comparison with motor and interneuron types in the vertebrate neural tube indicates conserved combinations, for example, of cell types cospecified by Gata1/2/3 and Tal transcription factors. These include V2b interneurons and the central spinal fluid-contacting Kolmer-Agduhr cells in the vertebrates, and several neuron types in the intermediate ventral ganglionic mass in the annelid. We propose that Kolmer-Agduhr cell-like mechanosensory neurons formed part of the mucociliary sole in protostome-deuterostome ancestors and diversified independently into several neuron types in annelid and vertebrate descendants.

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