Drosophila Lame duck, a novel member of the Gli superfamily, acts as a key regulator of myogenesis by controlling fusion-competent myoblast development

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4489-4500 ◽  
Author(s):  
Hong Duan ◽  
James B. Skeath ◽  
Hanh T. Nguyen
Keyword(s):  
Nuclear Localization ◽  
Skeletal Muscles ◽  
Muscle Fibers ◽  
Transcriptional Regulator ◽  
Dependent Manner ◽  
Fusion Genes ◽  
Lame Duck ◽  
Founder Cells ◽  
Fusion Competent Myoblasts ◽  
And Function

A hallmark of mature skeletal muscles is the presence of multinucleate muscle fibers. In Drosophila, the formation of muscle syncytia requires the cooperative participation of two types of myoblasts, founder cells and fusion-competent myoblasts. We show that a newly identified gene, lame duck (lmd), has an essential regulatory role in the specification and function of fusion-competent myoblasts. Embryos that lack lmd function show a loss of expression of two key differentiation and fusion genes, Mef2 and sticks-and-stones, in fusion-competent myoblasts and are completely devoid of multinucleate muscle fibers. By contrast, founder cells are specified and retain their capability to differentiate into mononucleate muscle cells. lmd encodes a novel member of the Gli superfamily of transcription factors and is expressed in fusion-competent myoblasts and their precursors in a Wingless- and Notch-dependent manner. The activity of the Lmd protein appears to be additionally controlled by its differential cytoplasmic versus nuclear localization. Results from an independent molecular screen for binding factors to a myoblast-specific Mef2 enhancer further demonstrate that Lmd is a direct transcriptional regulator of Mef2 in fusion-competent myoblasts.

scholarly journals Rewiring of an ancestral Tbx1/10-Ebf-Mrf network for pharyngeal muscle specification in distinct embryonic lineages

2016 ◽  
Author(s):  
Theadora Tolkin ◽  
Lionel Christiaen
Keyword(s):  
Molecular Basis ◽  
Skeletal Muscles ◽  
Temporal Order ◽  
Regulatory Factor ◽  
Pharyngeal Muscle ◽  
Linear Cascade ◽  
Founder Cells ◽  
Muscle Groups ◽  
And Function

Skeletal muscles arise from diverse embryonic origins, yet converge on common regulatory programs involving muscle regulatory factor (MRF)-family genes. Here, we compare the molecular basis of myogenesis in two separate muscle groups in the simple chordate Ciona: the atrial and oral siphon muscles. Here, we describe the ontogeny of OSM progenitors and characterize the clonal origins of OSM founders to compare mechanisms of OSM specification to what has been established for ASM. We determined that, as is the case in the ASM, Ebf and Tbx1/10 are both expressed and function upstream of Mrf in the OSM founder cells. However, regulatory relationships between Tbx1/10, Ebf and Mrf differ between the OSM and ASM lineages: while Tbx1/10, Ebf and Mrf form a linear cascade in the ASM, Ebf and Tbx1/10 are expressed in the inverse temporal order and are required together in order to activate Mrf in the OSM founder cells.

scholarly journals mTORC1 controls glycogen synthase kinase 3β nuclear localization and function

2018 ◽  
Author(s):  
Stephen J. Bautista ◽  
Ivan Boras ◽  
Adriano Vissa ◽  
Noa Mecica ◽  
Christopher M. Yip ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nuclear Localization ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Transcriptional Networks ◽  
Dependent Manner ◽  
Glycogen Synthase Kinase 3Β ◽  
Wide Range ◽  
Metabolic Conditions ◽  
And Function

AbstractGlycogen synthase kinase 3β (GSK3β) phosphorylates and regulates a wide range of substrates involved in diverse cellular functions. Some GSK3β substrates, such as c-myc and snail, are nuclear-resident transcription factors, suggesting possible control of GSK3β function by regulation of its nuclear localization. Inhibition of mechanistic target of rapamycin (mTORC1) led to partial redistribution of GSK3β from the cytosol to the nucleus, and GSK3β-dependent reduction of the expression of c-myc and snail. mTORC1 is controlled by metabolic cues, such as by AMP-activated protein kinase (AMPK) or amino acid abundance. Indeed AMPK activation or amino acid deprivation promoted GSK3β nuclear localization in an mTORC1-dependent manner. GSK3β was detected in several distinct endomembrane compartments, including lysosomes. Consistently, disruption of late endosomes/lysosomes through perturbation of Rab7 resulted in loss of GSK3β from lysosomes, and enhanced GSK3β nuclear localization as well as GSK3β-dependent reduction of c-myc levels. This indicates that GSK3β nuclear localization and function is suppressed by mTORC1, and suggests a new link between metabolic conditions sensed by mTORC1 and GSK3β-dependent regulation of transcriptional networks controlling biomass production.Summary statement (15-30 words)GSK3β nuclear localization and function is negatively regulated by the metabolic and mitogenic sensor mTORC1. mTORC1 control of GSK3β localization requires Rab7 and lysosomal membrane traffic.

HISTOMETRIC AND ULTRASTRUCTURAL ORGANIZATION OF THE NERVIMUSCULAR TERMINALS OF SKELETAL MUSCLES AT A HYPOKINESIA

2019 ◽  
pp. 55-63
Author(s):  
Z. M. Yaschyshyn ◽  
S. L. Popel
Keyword(s):  
Skeletal Muscles ◽  
Structural Adjustment ◽  
Muscle Fibers ◽  
Electron Microscopic Examination ◽  
Nerve Fibers ◽  
Ultrastructural Changes ◽  
Ultrastructural Organization ◽  
Electron Microscopic ◽  
Myelinated Nerve ◽  
Male Wistar Rats

The aim: to study the dynamics of histological and ultrastructural changes in muscle fibers and their neuromuscular endings under conditions of prolonged hypokinesia at different stages of ontogenesis. Methods. Studied skeletal muscles and their peripheral nervous apparatus of laboratory male Wistar rats aged 30 to 270 days. The restriction of motor activity was carried out in special canister cells for 30, 60, 90, and 240 days (5 animals for each term). To determine the type of muscle fiber, the Nahlas histochemical method was used, the Kulchitsky method was used to detect myelinated nerve fibers, the Bilshovsky-Gros method and the electron microscopic method to identify neuromuscular endings. Results. The data of histological and electron microscopic examination of skeletal muscle fibers and their neuromuscular endings under conditions of prolonged hypokinesia indicate their regular restructuring during the development of muscles, the formation of their synapses and structures that are associated with them at different stages of ontogenesis. Conclusion. The study provides an in-depth understanding of the relative frequency and nature of the disturbance of the neuromuscular endings during prolonged hypokinesia and its effect on the dynamics of structural adjustment of individual types of muscle fibers in ontogenesis.

HISTOMETRIC AND ULTRASTRUCTURAL ORGANIZATION OF THE NERVIMUSCULAR TERMINALS OF SKELETAL MUSCLES AT A HYPOKINESIA

2019 ◽  
pp. 55-63
Author(s):  
Z. M. Yaschyshyn ◽  
S. L. Popel
Keyword(s):  
Skeletal Muscles ◽  
Structural Adjustment ◽  
Muscle Fibers ◽  
Electron Microscopic Examination ◽  
Nerve Fibers ◽  
Ultrastructural Changes ◽  
Ultrastructural Organization ◽  
Electron Microscopic ◽  
Myelinated Nerve ◽  
Male Wistar Rats

The aim: to study the dynamics of histological and ultrastructural changes in muscle fibers and their neuromuscular endings under conditions of prolonged hypokinesia at different stages of ontogenesis. Methods. Studied skeletal muscles and their peripheral nervous apparatus of laboratory male Wistar rats aged 30 to 270 days. The restriction of motor activity was carried out in special canister cells for 30, 60, 90, and 240 days (5 animals for each term). To determine the type of muscle fiber, the Nahlas histochemical method was used, the Kulchitsky method was used to detect myelinated nerve fibers, the Bilshovsky-Gros method and the electron microscopic method to identify neuromuscular endings. Results. The data of histological and electron microscopic examination of skeletal muscle fibers and their neuromuscular endings under conditions of prolonged hypokinesia indicate their regular restructuring during the development of muscles, the formation of their synapses and structures that are associated with them at different stages of ontogenesis. Conclusion. The study provides an in-depth understanding of the relative frequency and nature of the disturbance of the neuromuscular endings during prolonged hypokinesia and its effect on the dynamics of structural adjustment of individual types of muscle fibers in ontogenesis.

scholarly journals Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 350
Author(s):  
Julianty Frost ◽  
Mark Frost ◽  
Michael Batie ◽  
Hao Jiang ◽  
Sonia Rocha
Keyword(s):  
Gene Expression ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Regulator ◽  
Hydroxylase Activity ◽  
Control Of Gene Expression ◽  
Prolyl Hydroxylases ◽  
Chromatin Organisation ◽  
Sense And Respond ◽  
Almost All ◽  
And Function

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.

Expression of the angiotensinogen gene is synergistically stimulated by 8-BrcAMP and Dex in opossum kidney cells

1995 ◽  
Vol 268 (1) ◽  
pp. R105-R111 ◽  
Author(s):  
M. Ming ◽  
T. T. Wang ◽  
S. Lachance ◽  
A. Delalandre ◽  
S. Carriere ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Dependent Manner ◽  
Fusion Genes ◽  
Opossum Kidney ◽  
Ok Cells ◽  
Angiotensinogen Gene ◽  
Opossum Kidney Cells ◽  
Dependent Protein ◽  
Flanking Region ◽  
Responsive Element

We transiently transfected fusion genes with the 5'-flanking region of the angiotensinogen gene linked to a bacterial chloramphenicol acetyltransferase (CAT) coding sequence as a reporter into opossum kidney (OK) cells. The addition of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) (10(-3)-10(-7) M) or forskolin (10(-9)-10(-5) M) stimulated the expression of the plasmid pOCAT [angiotensinogen nucleotide (N) -1498/+18] fusion gene in OK cells in a dose-dependent manner. The addition of dexamethasone (Dex) (10(-6) M) further enhanced the stimulatory effect of 8-BrcAMP or forskolin, whereas the addition of (R)-p-adenosine 3',5'-cyclic monophosphorothioate [(Rp)-cAMP[S], an inhibitor of cAMP-dependent protein kinase A, I and II] blocked the stimulatory effect of 8-BrcAMP. Furthermore, the addition of 8-BrcAMP (10(-3) M) or Dex (10(-6) M) or a combination of both stimulated the expression of pOCAT (angiotensinogen N -1138/+18), pOCAT (angiotensinogen N -960/+18), pOCAT (angiotensinogen N -814/+18), and pOCAT (angiotensinogen N -688/+18), but had no effect on the expression of pOCAT (angiotensinogen N -280/+18), pOCAT (angiotensinogen N -198/+18), pOCAT (angiotensinogen N -110/+18), pOCAT (angiotensinogen N -53/+18), and pOCAT (angiotensinogen N -35/+18). To further localize the putative cAMP-responsive element (CRE) in the angiotensinogen gene, we constructed fusion genes by inserting the DNA fragments angiotensinogen N -814 to N -689, angiotensinogen N -814 to N -761, and angiotensinogen N -760 to N -689 of the 5'-flanking region of the angiotensinogen gene upstream of the thymidine kinase (TK) promoter fused to a CAT gene and introduced them into OK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Positive cross talk between protein kinase D and β-catenin in intestinal epithelial cells: impact on β-catenin nuclear localization and phosphorylation at Ser552

2016 ◽  
Vol 310 (7) ◽  
pp. C542-C557 ◽  
Author(s):  
Jia Wang ◽  
Liang Han ◽  
James Sinnett-Smith ◽  
Li-Li Han ◽  
Jan V. Stevens ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Transgenic Mice ◽  
Nuclear Localization ◽  
Cross Talk ◽  
Intestinal Epithelial Cells ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Ang Ii ◽  
Potent Inducer

Given the fundamental role of β-catenin signaling in intestinal epithelial cell proliferation and the growth-promoting function of protein kinase D1 (PKD1) in these cells, we hypothesized that PKDs mediate cross talk with β-catenin signaling. The results presented here provide several lines of evidence supporting this hypothesis. We found that stimulation of intestinal epithelial IEC-18 cells with the G protein-coupled receptor (GPCR) agonist angiotensin II (ANG II), a potent inducer of PKD activation, promoted endogenous β-catenin nuclear localization in a time-dependent manner. A significant increase was evident within 1 h of ANG II stimulation ( P < 0.01), peaked at 4 h ( P < 0.001), and declined afterwards. GPCR stimulation also induced a marked increase in β-catenin-regulated genes and phosphorylation at Ser552 in intestinal epithelial cells. Exposure to preferential inhibitors of the PKD family (CRT006610 or kb NB 142-70) or knockdown of the isoforms of the PKD family prevented the increase in β-catenin nuclear localization and phosphorylation at Ser552 in response to ANG II. GPCR stimulation also induced the formation of a complex between PKD1 and β-catenin, as shown by coimmunoprecipitation that depended on PKD1 catalytic activation, as it was abrogated by cell treatment with PKD family inhibitors. Using transgenic mice that express elevated PKD1 protein in the intestinal epithelium, we detected a marked increase in the localization of β-catenin in the nucleus of crypt epithelial cells in the ileum of PKD1 transgenic mice, compared with nontransgenic littermates. Collectively, our results identify a novel cross talk between PKD and β-catenin in intestinal epithelial cells, both in vitro and in vivo.

scholarly journals Spatiotemporal dynamics of OCT4 protein localization during preimplantation development in mice

Reproduction ◽  
2016 ◽  
Vol 152 (5) ◽  
pp. 417-430 ◽  
Author(s):  
Atsushi Fukuda ◽  
Atsushi Mitani ◽  
Toshiyuki Miyashita ◽  
Hisato Kobayashi ◽  
Akihiro Umezawa ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Splice Variants ◽  
Protein Localization ◽  
Preimplantation Development ◽  
Preimplantation Embryos ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Cell Stage ◽  
Protein Levels ◽  
Oct4 Protein

Spatiotemporal expression of transcription factors is crucial for genomic reprogramming. Pou5f1 (Oct4) is an essential transcription factor for reprogramming. A recent study reported that OCT4A, which is crucial for establishment and maintenance of pluripotent cells, is expressed in oocytes, but maternal OCT4A is dispensable for totipotency induction. Whereas another study reported that OCT4B, which is not related to pluripotency, is predominantly expressed instead of OCT4A during early preimplantation phases in mice. To determine the expression states of OCT4 in murine preimplantation embryos, we conducted in-depth expression and functional analyses. We found that pluripotency-related OCT4 mainly localizes to the cytoplasm in early preimplantation phases, with no major nuclear localization until the 8–16-cell stage despite high expression in both oocytes and early embryos. RNA-sequencing analysis using oocytes and early preimplantation embryos could not identify the splice variants creating alternative forms of OCT4 protein. Forced expression of OCT4 in zygotes by the injection of polyadenylated mRNA clearly showed nuclear localization of OCT4 protein around 3–5-fold greater than physiological levels and impaired developmental competency in a dose-dependent manner. Embryos with modest overexpression of OCT4 could develop to the 16-cell stage; however, more than 50% of the embryos were arrested at this stage, similar to the results for OCT4 depletion. In contrast, extensive overexpression of OCT4 resulted in complete arrest at the 2-cell stage accompanied by downregulation of zygotically activated genes and repetitive elements related to the totipotent state. These results demonstrated that OCT4 protein localization was spatiotemporally altered during preimplantation development, and strict control of Oct4 protein levels was essential for proper totipotential reprogramming.

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