Decision letter: A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

In most vertebrates, the upper digestive tract is composed of muscularized jaws linked to the esophagus that permits food ingestion and swallowing. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we show that the transcription factors Tbx1 and Isl1 are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies point to MET/HGF signaling for antero-posterior migration of esophagus muscle progenitors, where Hgf ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Our findings establish a Tbx1-Isl1-Met genetic hierarchy that uniquely regulates esophagus myogenesis and identify distinct genetic signatures that can be used as framework to interpret pathologies arising within CPM derivatives.

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Muscle LIM Proteins Are Associated with Muscle Sarcomeres and Require dMEF2 for Their Expression during DrosophilaMyogenesis

Molecular Biology of the Cell ◽

10.1091/mbc.10.7.2329 ◽

1999 ◽

Vol 10 (7) ◽

pp. 2329-2342 ◽

Cited By ~ 38

Author(s):

Beth E. Stronach ◽

Patricia J. Renfranz ◽

Brenda Lilly ◽

Mary C. Beckerle

Keyword(s):

Muscle Development ◽

Target Genes ◽

Striated Muscle ◽

Myogenic Differentiation ◽

Muscle Differentiation ◽

Epistasis Analysis ◽

Lim Proteins ◽

Muscle Lim Proteins ◽

Genetic Hierarchy

A genetic hierarchy of interactions, involving myogenic regulatory factors of the MyoD and myocyte enhancer-binding 2 (MEF2) families, serves to elaborate and maintain the differentiated muscle phenotype through transcriptional regulation of muscle-specific target genes. Much work suggests that members of the cysteine-rich protein (CRP) family of LIM domain proteins also play a role in muscle differentiation; however, the specific functions of CRPs in this process remain undefined. Previously, we characterized two members of the Drosophila CRP family, the muscle LIM proteins Mlp60A and Mlp84B, which show restricted expression in differentiating muscle lineages. To extend our analysis ofDrosophila Mlps, we characterized the expression of Mlps in mutant backgrounds that disrupt specific aspects of muscle development. We show a genetic requirement for the transcription factor dMEF2 in regulating Mlp expression and an ability of dMEF2 to bind, in vitro, to consensus MEF2 sites derived from those present inMlp genomic sequences. These data suggest that theMlp genes may be direct targets of dMEF2 within the genetic hierarchy controlling muscle differentiation. Mutations that disrupt myoblast fusion fail to affect Mlp expression. In later stages of myogenic differentiation, which are dedicated primarily to assembly of the contractile apparatus, we analyzed the subcellular distribution of Mlp84B in detail. Immunofluorescent studies revealed the localization of Mlp84B to muscle attachment sites and the periphery of Z-bands of striated muscle. Analysis of mutations that affect expression of integrins and α-actinin, key components of these structures, also failed to perturb Mlp84B distribution. In conclusion, we have used molecular epistasis analysis to position Mlp function downstream of events involving mesoderm specification and patterning and concomitant with terminal muscle differentiation. Furthermore, our results are consistent with a structural role for Mlps as components of muscle cytoarchitecture.

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Author response: A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

10.7554/elife.47460.024 ◽

2019 ◽

Cited By ~ 1

Author(s):

Glenda Comai ◽

Eglantine Heude ◽

Sebastian Mella ◽

Sylvain Paisant ◽

Francesca Pala ◽

...

Keyword(s):

Striated Muscle ◽

Author Response ◽

Genetic Hierarchy

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A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

10.1101/600841 ◽

2019 ◽

Author(s):

Glenda Comai ◽

Églantine Heude ◽

Sebastien Mella ◽

Sylvain Paisant ◽

Francesca Pala ◽

...

Keyword(s):

Skeletal Muscle ◽

Smooth Muscle ◽

Striated Muscle ◽

Striated Muscles ◽

Loss Of Function ◽

Pharmacological Studies ◽

Posterior Migration ◽

Functional Relevance ◽

Genetic Signatures ◽

Genetic Hierarchy

SUMMARYIn most vertebrates, the upper digestive tract is composed of muscularised jaws linked to the esophagus that permit food uptake and swallowing. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we show that the transcription factors Tbx1 and Isl1 are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies point to Met/HGF signalling for antero-posterior migration of esophagus muscle progenitors, where HGF ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Our findings establish a Tbx1-Isl1-Met genetic hierarchy that uniquely regulate esophagus myogenesis and identify distinct genetic signatures that can be used as a framework to interpret pathologies arising within CPM derivatives.

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Ultrastructural Localization of Acid Mucosubstance in Skeletal Muscle

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100060271 ◽

1967 ◽

Vol 25 ◽

pp. 52-53 ◽

Cited By ~ 2

Author(s):

William J. Dougherty ◽

Samuel S. Spicer

Keyword(s):

Striated Muscle ◽

Divalent Cations ◽

Ultrastructural Localization ◽

Major Elements ◽

Frozen Sections ◽

Thorium Dioxide ◽

Iron Solution ◽

Coupling System ◽

Psoas Muscles ◽

Formalin Fixed

In recent years, considerable attention has focused on the morphological nature of the excitation-contraction coupling system of striated muscle. Since the study of Porter and Palade, it has become evident that the sarcoplastic reticulum (SR) and transverse tubules constitute the major elements of this system. The problem still exists, however, of determining the mechamisms by which the signal to interdigitate is presented to the thick and thin myofilaments. This problem appears to center on the movement of Ca++ions between myofilaments and SR. Recently, Philpott and Goldstein reported acid mucosubstance associated with the SR of fish branchial muscle using the colloidal thorium dioxide technique, and suggested that this material may serve to bind or release divalent cations such as Ca++. In the present study, Hale's iron solution adapted to electron microscopy was applied to formalin-fixed myofibrils isolated from glycerol-extracted rabbit psoas muscles and to frozen sections of formalin-fixed rat psoas muscles.

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Quantitative Freeze Fracture Studies of Gap Junctions in Somatic Cell Hybrids, Their Parents, and Revertants

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010009107x ◽

1976 ◽

Vol 34 ◽

pp. 218-219

Author(s):

W. J. Larsen ◽

R. Azarnia ◽

W. R. Loewenstein

Keyword(s):

Gap Junctions ◽

Striated Muscle ◽

Freeze Fracture ◽

Cell Movement ◽

Dye Molecules ◽

Somatic Cell Hybrids ◽

Cell Coupling ◽

Normal Cells ◽

Mediate Cell ◽

Almost All

Although the physiological significance of the gap junction remains unspecified, these membrane specializations are now recognized as common to almost all normal cells (excluding adult striated muscle and some nerve cells) and are found in organisms ranging from the coelenterates to man. Since it appears likely that these structures mediate the cell-to-cell movement of ions and small dye molecules in some electrical tissues, we undertook this study with the objective of determining whether gap junctions in inexcitable tissues also mediate cell-to-cell coupling.To test this hypothesis, a coupling, human Lesh-Nyhan (LN) cell was fused with a non-coupling, mouse cl-1D cell, and the hybrids, revertants, and parental cells were analysed for coupling with respect both to ions and fluorescein and for membrane junctions with the freeze fracture technique.

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Orientation of actin filaments during motion in motility assay

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100136635 ◽

1995 ◽

Vol 53 ◽

pp. 52-53

Author(s):

J. Borejdo ◽

S. Burlacu

Keyword(s):

Actin Filaments ◽

Thin Filament ◽

Striated Muscle ◽

Myosin Head ◽

Classical Method ◽

Polarization Of Fluorescence ◽

Single Protein ◽

Intracellular Organelles ◽

Change Orientation ◽

Active Entity

Polarization of fluorescence is a classical method to assess orientation or mobility of macromolecules. It has been a common practice to measure polarization of fluorescence through a microscope to characterize orientation or mobility of intracellular organelles, for example anisotropic bands in striated muscle. Recently, we have extended this technique to characterize single protein molecules. The scientific question concerned the current problem in muscle motility: whether myosin heads or actin filaments change orientation during contraction. The classical view is that the force-generating step in muscle is caused by change in orientation of myosin head (subfragment-1 or SI) relative to the axis of thin filament. The molecular impeller which causes this change resides at the interface between actin and SI, but it is not clear whether only the myosin head or both SI and actin change orientation during contraction. Most studies assume that observed orientational change in myosin head is a reflection of the fact that myosin is an active entity and actin serves merely as a passive "rail" on which myosin moves.

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The Advantages of Cryotechniques: Application To Bioluminescent Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010018118x ◽

1990 ◽

Vol 48 (1) ◽

pp. 486-487

Author(s):

Gisèle Nicolas ◽

Jean-Marie Bassot ◽

Marie-Thérèse Nicolas

Keyword(s):

Endoplasmic Reticulum ◽

Striated Muscle ◽

Light Emission ◽

Stable State ◽

Freeze Substitution ◽

Initial Step ◽

Point Of Interest ◽

Cell Components ◽

Excellent Preservation ◽

External Water

The use of fast-freeze fixation (FFF) followed by freeze-substitution (FS) brings substantial advantages which are due to the extreme rapidity of this fixation compared to the conventional one. The initial step, FFF, physically immobilizes most molecules and therefore arrests the biological reactions in a matter of milliseconds. The second step, FS, slowly removes the water content still in solid state and, at the same time, chemically fixes the other cell components in absence of external water. This procedure results in an excellent preservation of the ultrastructure, avoids osmotic artifacts,maintains in situ most soluble substances and keeps up a number of cell activities including antigenicities. Another point of interest is that the rapidity of the initial immobilization enables the capture of unstable structures which, otherwise, would slip towards a more stable state. When combined with electrophysiology, this technique arrests the ultrastructural modifications at a well defined state, allowing a precise timing of the events.We studied the epithelium of the elytra of the scale-worm, Harmothoe lunulata which has excitable, conductible and bioluminescent properties. The intracellular sites of the light emission are paracrystals of endoplasmic reticulum (PER), named photosomes (Fig.1). They are able to flash only when they are coupled with plasma membrane infoldings by dyadic or triadic junctions (Fig.2) basically similar to those of the striated muscle fibers. We have studied them before, during and after stimulation. FFF-FS showed that these complexes are labile structures able to diffentiate and dedifferentiate within milliseconds. Moreover, a transient network of endoplasmic reticulum was captured which we have named intermediate endoplasmic reticulum (IER) surrounding the PER (Fig.1). Numerous gap junctions are found in the membranous infoldings of the junctional complexes (Fig.3). When cryofractured, they cleave unusually (Fig.4-5). It is tempting to suggest that they play an important role in the conduction of the excitation.

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POPDC proteins and cardiac function

Biochemical Society Transactions ◽

10.1042/bst20190249 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1393-1404 ◽

Cited By ~ 4

Author(s):

Thomas Brand

Keyword(s):

Potential Role ◽

Striated Muscle ◽

Short Review ◽

Effector Proteins ◽

Muscle Disease ◽

Disease Genes ◽

Protein Protein Interaction ◽

Interaction Partners ◽

And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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Post-Transcriptional Regulation of Cardiac Sarcomere Protein Titin Through 3’ Untranslated Regions

Vanderbilt Undergraduate Research Journal ◽

10.15695/vurj.v9i0.3772 ◽

2013 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Tara A Shrout

Keyword(s):

Gene Expression ◽

Transcriptional Control ◽

Striated Muscle ◽

Binding Capacity ◽

Structural Features ◽

Neonatal Rat ◽

Regulatory Control ◽

Untranslated Regions ◽

Luciferase Reporter ◽

Regulatory Effects

Titin is the largest known protein in the human body, and forms the backbone of all striated muscle sarcomeres. The elastic nature of titin is an important component of muscle compliance and functionality. A significant amount of energy is expended to synthesize titin, thus we postulate that titin gene expression is under strict regulatory control in order to conserve cellular resources. In general, gene expression is mediated in part by post-transcriptional control elements located within the 5’ and 3’ untranslated regions (UTRs) of mature mRNA. The 3’UTR in particular contains structural features that affect binding capacity to other RNA components, such as MicroRNA, which control mRNA localization, translation, and degradation. The degree and significance of the regulatory effects mediated by two determined variants of titin’s 3’ UTR were evaluated in Neonatal Rat Ventricular Myocyte and Human Embryonic Kidney cell lines. Recombinant plasmids to transfect these cells lines were engineered by insertion of the variant titin 3’UTR 431- and 1047-base pairs sequences into luciferase reporter vectors. Expression due to an unaltered reporter vector served as the control. Quantitative changes in luciferase activity due to the recombinants proportionally represented the effect titin’s respective 3’UTR conferred on downstream post-transcriptional expression relative to the control. The effect due to titin’s shorter 3’UTR sequence was inconclusive; however, results illustrated that titin’s longer 3’UTR sequence caused a 35 percent decrease in protein expression. Secondary structural analysis of the two sequences revealed differential folding patterns that affect the stability and degree of MicroRNA-binding within titin’s variant 3’UTR sequences.

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