scholarly journals DamID identifies targets of CEH-60/PBX that are associated with neuron development and muscle structure in Caenorhabditis elegans

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242939
Author(s):  
Pieter Van de Walle ◽  
Celia Muñoz-Jiménez ◽  
Peter Askjaer ◽  
Liliane Schoofs ◽  
Liesbet Temmerman
Keyword(s):  
Caenorhabditis Elegans ◽  
Muscle Development ◽  
Specific Gene ◽  
Neuron Development ◽  
Interaction Sites ◽  
Muscle Structure ◽  
Pharyngeal Muscles ◽  
Functional Consequences ◽  
Living Organisms ◽  
And Function

Transcription factors govern many of the time- and tissue-specific gene expression events in living organisms. CEH-60, a homolog of the TALE transcription factor PBX in vertebrates, was recently characterized as a new regulator of intestinal lipid mobilization in Caenorhabditis elegans. Because CEH-60’s orthologs and paralogs exhibit several other functions, notably in neuron and muscle development, and because ceh-60 expression is not limited to the C. elegans intestine, we sought to identify additional functions of CEH-60 through DNA adenine methyltransferase identification (DamID). DamID identifies protein-genome interaction sites through GATC-specific methylation. We here report 872 putative CEH-60 gene targets in young adult animals, and 587 in L2 larvae, many of which are associated with neuron development or muscle structure. In light of this, we investigate morphology and function of ceh-60 expressing AWC neurons, and contraction of pharyngeal muscles. We find no clear functional consequences of loss of ceh-60 in these assays, suggesting that in AWC neurons and pharyngeal muscle, CEH-60 function is likely more subtle or redundant with other factors.

Growing healthy muscles to optimise metabolic health into adult life

2014 ◽  
Vol 5 (6) ◽  
pp. 420-434 ◽  
Author(s):  
S. A. Bayol ◽  
C. R. Bruce ◽  
G. D. Wadley
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Maternal Obesity ◽  
Adult Life ◽  
Metabolic Health ◽  
Skeletal Muscle Development ◽  
Pregnancy And Lactation ◽  
Functional Consequences ◽  
And Function

The importance of skeletal muscle for metabolic health and obesity prevention is gradually gaining recognition. As a result, interventions are being developed to increase or maintain muscle mass and metabolic function in adult and elderly populations. These interventions include exercise, hormonal and nutritional therapies. Nonetheless, growing evidence suggests that maternal malnutrition and obesity during pregnancy and lactation impede skeletal muscle development and growth in the offspring, with long-term functional consequences lasting into adult life. Here we review the role of skeletal muscle in health and obesity, providing an insight into how this tissue develops and discuss evidence that maternal obesity affects its development, growth and function into adult life. Such evidence warrants the need to develop early life interventions to optimise skeletal muscle development and growth in the offspring and thereby maximise metabolic health into adult life.

scholarly journals Hypergravity hinders axonal development of motor neurons in Caenorhabditis elegans

2016 ◽  
Author(s):  
Saraswathi Subbammal Kalichamy ◽  
Tong Young Lee ◽  
Kyoung-hye Yoon ◽  
Jin Il Lee
Keyword(s):  
Caenorhabditis Elegans ◽  
Motor Neurons ◽  
Muscle Development ◽  
Model Organism ◽  
Dorsal Side ◽  
Body Region ◽  
Muscle Physiology ◽  
Neuron Development ◽  
Axonal Projections ◽  
Axonal Defects

As space flight becomes more accessible in the future, humans will be exposed to gravity conditions other than our 1G environment on Earth. Changes in physiology and anatomy in altered gravity conditions have long been observed, especially the loss of muscle mass during long-term space habitation, the reason for which is not fully understood. Although much effort has gone into studying the effects of gravity in muscle physiology, its effect on the development of neurons has not been thoroughly assessed. Using the nematode model organism Caenorhabditis elegans, we examined changes in response to hypergravity in the development of the 19 GABAergic DD/VD motor neurons that innervate body muscle. We found that a high gravity force above 10G significantly increases the number of animals with defects in the development of axonal projections from the DD/VD neurons. We showed that a critical period of hypergravity exposure during the embryonic/early larval stage was sufficient to induce defects. While characterizing the nature of the axonal defects, we found that in normal 1G gravity conditions, DD/VD axonal defects occasionally occurred, with the majority of defects occurring on the dorsal side of the animal and in the mid-body region, and a significantly higher rate of error in the 13 VD axons than the 6 DD axons. Hypergravity exposure increased the rate of DD/VD axonal defects, but did not change the distribution or the characteristics of the defects. Our study demonstrates that in addition to gravity’s effects on muscle development, gravity can also impact motor neuron development.

The Caenorhabditis elegans NK-2 homeobox gene ceh-22 activates pharyngeal muscle gene expression in combination with pha-1 and is required for normal pharyngeal development

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 3965-3973 ◽  
Author(s):  
P.G. Okkema ◽  
E. Ha ◽  
C. Haun ◽  
W. Chen ◽  
A. Fire
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Muscle Development ◽  
Synergistic Effects ◽  
Chain Gene ◽  
Loss Of Function ◽  
Pharyngeal Muscle ◽  
Muscle Gene Expression ◽  
Pharyngeal Muscles ◽  
Muscle Gene

Pharyngeal muscle development in the nematode Caenorhabditis elegans appears to share similarities with cardiac muscle development in other species. We have previously described CEH-22, an NK-2 class homeodomain transcription factor similar to Drosophila tinman and vertebrate Nkx2-5, which is expressed exclusively in the pharyngeal muscles. In vitro, CEH-22 binds the enhancer from myo-2, a pharyngeal muscle-specific myosin heavy chain gene. In this paper, we examine the role CEH-22 plays in pharyngeal muscle development and gene activation by (a) ectopically expressing ceh-22 in transgenic C. elegans and (b) examining the phenotype of a ceh-22 loss-of-function mutant. These experiments indicate that CEH-22 is an activator of myo-2 expression and that it is required for normal pharyngeal muscle development. However, ceh-22 is necessary for neither formation of the pharyngeal muscles, nor for myo-2 expression. Our data suggest parallel and potentially compensating pathways contribute to pharyngeal muscle differentiation. We also examine the relationship between ceh-22 and the pharyngeal organ-specific differentiation gene pha-1. Mutations in ceh-22 and pha-1 have strongly synergistic effects on pharyngeal muscle gene expression; in addition, a pha-1 mutation enhances the lethal phenotype caused by a mutation in ceh-22. Wild-type pha-1 is not required for the onset of ceh-22 expression but it appears necessary for maintained expression of ceh-22.

scholarly journals Hypergravity hinders axonal development of motor neurons in Caenorhabditis elegans

2016 ◽  
Author(s):  
Saraswathi Subbammal Kalichamy ◽  
Tong Young Lee ◽  
Kyoung-hye Yoon ◽  
Jin Il Lee
Keyword(s):  
Caenorhabditis Elegans ◽  
Motor Neurons ◽  
Muscle Development ◽  
Model Organism ◽  
Dorsal Side ◽  
Body Region ◽  
Muscle Physiology ◽  
Neuron Development ◽  
Axonal Projections ◽  
Axonal Defects

As space flight becomes more accessible in the future, humans will be exposed to gravity conditions other than our 1G environment on Earth. Changes in physiology and anatomy in altered gravity conditions have long been observed, especially the loss of muscle mass during long-term space habitation, the reason for which is not fully understood. Although much effort has gone into studying the effects of gravity in muscle physiology, its effect on the development of neurons has not been thoroughly assessed. Using the nematode model organism Caenorhabditis elegans, we examined changes in response to hypergravity in the development of the 19 GABAergic DD/VD motor neurons that innervate body muscle. We found that a high gravity force above 10G significantly increases the number of animals with defects in the development of axonal projections from the DD/VD neurons. We showed that a critical period of hypergravity exposure during the embryonic/early larval stage was sufficient to induce defects. While characterizing the nature of the axonal defects, we found that in normal 1G gravity conditions, DD/VD axonal defects occasionally occurred, with the majority of defects occurring on the dorsal side of the animal and in the mid-body region, and a significantly higher rate of error in the 13 VD axons than the 6 DD axons. Hypergravity exposure increased the rate of DD/VD axonal defects, but did not change the distribution or the characteristics of the defects. Our study demonstrates that in addition to gravity’s effects on muscle development, gravity can also impact motor neuron development.

scholarly journals A VISIBLE ALLELE OF THE MUSCLE GENE sup-10 X OF C. ELEGANS

Genetics ◽  
1986 ◽  
Vol 113 (1) ◽  
pp. 63-72
Author(s):  
Iva Greenwald ◽  
H Robert Horvitz
Keyword(s):  
Caenorhabditis Elegans ◽  
Protein Complex ◽  
Structure And Function ◽  
The Other ◽  
Wild Type ◽  
C Elegans ◽  
Muscle Structure ◽  
New Gene ◽  
Muscle Gene ◽  
And Function

ABSTRACT In this paper, we extend our previous analyses of a set of genes in Caenorhabditis elegans that are involved in muscle structure and function: unc-93 III, sup-9 II, sup-10 X and sup-11 I. We describe an unusual, visible allele of sup-10, examine how this allele interacts genetically with mutations in other genes of this set and propose that the wild-type products of the unc-93 and sup-10 loci may be components of a protein complex. We also describe a new gene of this set, sup-18 III, and the interaction of sup-18 alleles with mutations in the other genes.

scholarly journals Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations

1994 ◽  
Vol 124 (4) ◽  
pp. 475-490 ◽  
Author(s):  
BD Williams ◽  
RH Waterston
Keyword(s):  
Caenorhabditis Elegans ◽  
Thin Filament ◽  
Muscle Development ◽  
Thin Filaments ◽  
Myosin Heavy Chain Isoform ◽  
Filament Assembly ◽  
Dense Bodies ◽  
Phenotype Characteristic ◽  
Specific Muscle ◽  
And Function

By taking advantage of a lethal phenotype characteristic of Caenorhabditis elegans embryos that fail to move, we have identified 13 genes required for muscle assembly and function and discovered a new lethal class of alleles for three previously known muscle-affecting genes. By staining mutant embryos for myosin and actin we have recognized five distinct classes of genes: mutations in four genes disrupt the assembly of thick and thin filaments into the myofilament lattice as well as the polarized location of these components to the sarcolemma. Mutations in another three genes also disrupt thick and thin filament assembly, but allow proper polarization of lattice components based on the myosin heavy chain isoform that we analyzed. Another two classes of genes are defined by mutations with principal effects on thick or thin filament assembly into the lattice, but not both. The final class includes three genes in which mutations cause relatively minor defects in lattice assembly. Failure of certain mutants to stain with antibodies to specific muscle cell antigens suggest that two genes associated with severe disruptions of myofilament lattice assembly may code for components of the basement membrane and the sarcolemma that are concentrated where dense bodies (Z-line analogs) and M-lines attach to the cell membrane. Similar evidence suggests that one of the genes associated with mild effects on lattice assembly may code for tropomyosin. Many of the newly identified genes are likely to play critical roles in muscle development and function.

scholarly journals Disruption of Caenorhabditis elegans Muscle Structure and Function Caused by Mutation of Troponin I

2004 ◽  
Vol 86 (2) ◽  
pp. 991-1001 ◽  
Author(s):  
A.K. Burkeen ◽  
S.L. Maday ◽  
K.K. Rybicka ◽  
J.A. Sulcove ◽  
J. Ward ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Troponin I ◽  
Structure And Function ◽  
Muscle Structure ◽  
And Function

scholarly journals Essential Role of Septin 7 in Skeletal Muscle Structure and Function

2020 ◽  
Vol 118 (3) ◽  
pp. 258a
Author(s):  
Laszlo Csernoch ◽  
Mónika Gönczi ◽  
Zsolt Ráduly ◽  
László Szabó ◽  
Nóra Dobrosi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Essential Role ◽  
Structure And Function ◽  
Muscle Structure ◽  
And Function

scholarly journals NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5902
Author(s):  
Stefan Nagel ◽  
Claudia Pommerenke ◽  
Corinna Meyer ◽  
Hans G. Drexler
Keyword(s):  
Dendritic Cells ◽  
Transcription Factors ◽  
Cell Lines ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Homeobox Gene ◽  
Leukemia Cell Line ◽  
Specific Gene ◽  
Rna Seq ◽  
And Function

Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.

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