Molecular analysis of smooth muscle development in the mouse
01 Nov 1995-Developmental Dynamics (Wiley Subscription Services, Inc., A Wiley Company)-Vol. 204, Iss: 3, pp 278-290
TL;DR: The results of this study indicate that distinct cellular phenotypes are involved in smooth muscle myogenesis and suggest that organ‐specific mechanisms might exist for the initiation of smooth muscle development in vivo.
Abstract: Little is currently known regarding the ontogeny of smooth muscle tissues during normal mammalian development. The alpha-smooth muscle and gamma-smooth muscle isoactins have been shown to be excellent molecular markers of smooth muscle cell phenotype. This study characterizes both the temporal and spatial patterns of alpha-smooth muscle and gamma-smooth muscle isoactin expression in the developing mouse. In situ analysis was performed on serial sections of whole mouse embryos on embryonic day 9, 11, 13, 15, and 17 using alpha-smooth muscle and gamma-smooth muscle isoactin-specific riboprobes. Distinct temporal and spatial patterns of alpha-smooth muscle and gamma-smooth muscle isoactin gene expression were observed in the developing gastrointestinal tract, urogenital tract, respiratory tract, and vascular system. Independent expression of the alpha-smooth muscle isoactin was observed during the early stages of skeletal, cardiac, and smooth muscle myogenesis as well as in a novel subset of distinct organs including the postnatal component of the hindgut, allantois, and primitive placenta. The results of this study indicate that distinct cellular phenotypes are involved in smooth muscle myogenesis and suggest that organ-specific mechanisms might exist for the initiation of smooth muscle development in vivo. In addition, the pattern of independent alpha-smooth muscle isoactin expression observed in this study provides novel information regarding the early stages of hindgut and placental development, and suggests that a common functional phenotype may be associated with the early stages of skeletal, cardiac, and smooth muscle myogenesis.
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TL;DR: Findings point to these miRNAs as critical components of an SRF-dependent myogenic transcriptional circuit in orchestrating cardiac development, gene expression, and function.
Abstract: MicroRNAs (miRNAs) modulate gene expression by inhibiting mRNA translation and promoting mRNA degradation, but little is known of their potential roles in organ formation or function. miR-133a-1 and miR-133a-2 are identical, muscle-specific miRNAs that are regulated during muscle development by the SRF transcription factor. We show that mice lacking either miR-133a-1 or miR-133a-2 are normal, whereas deletion of both miRNAs causes lethal ventricular-septal defects in approximately half of double-mutant embryos or neonates; miR-133a double-mutant mice that survive to adulthood succumb to dilated cardiomyopathy and heart failure. The absence of miR-133a expression results in ectopic expression of smooth muscle genes in the heart and aberrant cardiomyocyte proliferation. These abnormalities can be attributed, at least in part, to elevated expression of SRF and cyclin D2, which are targets for repression by miR-133a. These findings reveal essential and redundant roles for miR-133a-1 and miR-133a-2 in orchestrating cardiac development, gene expression, and function and point to these miRNAs as critical components of an SRF-dependent myogenic transcriptional circuit.
788 citations
Cites background from "Molecular analysis of smooth muscle..."
...Smooth muscle genes are transiently expressed in the heart during embryogenesis (Ruzicka and Schwartz 1988; McHugh 1995; Li et al. 1996)....
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TL;DR: The roles of miRNAs as regulators of cardiac form and function, unresolved questions in the field, and issues for the future are discussed.
480 citations
Cites background from "Molecular analysis of smooth muscle..."
...During normal heart development, smooth muscle genes are transiently expressed at the heart tube stage (Li et al., 1996; McHugh, 1995; Ruzicka and Schwartz, 1988)....
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TL;DR: Data indicate that smooth muscle-specific Nox1 overexpression augments the oxidative, pressor, and hypertrophic responses to Ang II, supporting the concept that medial Nox 1 participates in the development of cardiovascular pathologies.
Abstract: Background— Reactive oxygen species (ROS) have been implicated in the development of cardiovascular pathologies. NAD(P)H oxidases (Noxes) are major sources of reactive oxygen species in the vessel wall, but the importance of individual Nox homologues in specific layers of the vascular wall is unclear. Nox1 upregulation has been implicated in cardiovascular pathologies such as hypertension and restenosis. Methods and Results— To investigate the pathological role of Nox1 upregulation in vascular smooth muscle, transgenic mice overexpressing Nox1 in smooth muscle cells (TgSMCnox1) were created, and the impact of Nox1 upregulation on the medial hypertrophic response during angiotensin II (Ang II)–induced hypertension was studied. These mice have increased expression of Nox1 protein in the vasculature, which is accompanied by increased superoxide production. Infusion of Ang II (0.7 mg/kg per day) into these mice for 2 weeks led to a potentiation of superoxide production compared with similarly treated negative...
414 citations
TL;DR: In vivo and in vitro analyses demonstrate that sonic hedgehog promotes mesenchymal cell proliferation, regulates the timing of differentiation of smooth muscle progenitor cells, and sets the pattern of mesenchyme differentiation through its dose-dependent inhibition of smoother muscle formation.
Abstract: Signaling by the ureteric bud epithelium is essential for survival,
proliferation and differentiation of the metanephric mesenchyme during kidney
development. Most studies that have addressed ureteric signaling have focused
on the proximal, branching, ureteric epithelium. We demonstrate that sonic
hedgehog is expressed in the ureteric epithelium of the distal, non-branching
medullary collecting ducts and continues into the epithelium of the ureter
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the urinary outflow tract that connects the kidney with the bladder.
Upregulation of patched 1, the sonic hedgehog receptor and a downstream target
gene of the signaling pathway in the mesenchyme surrounding the distal
collecting ducts and the ureter suggests that sonic hedgehog acts as a
paracrine signal. In vivo and in vitro analyses demonstrate that sonic
hedgehog promotes mesenchymal cell proliferation, regulates the timing of
differentiation of smooth muscle progenitor cells, and sets the pattern of
mesenchymal differentiation through its dose-dependent inhibition of smooth
muscle formation. In addition, we also show that bone morphogenetic protein 4
is a downstream target gene of sonic hedgehog signaling in kidney stroma and
ureteral mesenchyme, but does not mediate the effects of sonic hedgehog in the
control of mesenchymal proliferation.
410 citations
Cites background from "Molecular analysis of smooth muscle..."
...Smooth muscle forms from condensed mesenchyme that underlies the urothelium in the ureter and the renal pelvis (McHugh, 1995)....
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...…smooth muscle formation in a dosedependent manner Smooth muscle formation in the ureter has been reported to occur in cells immediately adjacent to the urothelium, a similar position to smooth muscle in the respiratory system (McHugh, 1995), which is also Shh dependent (Pepicelli et al., 1998)....
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...Smooth muscle differentiation in the ureteral mesenchyme is delayed in Shh mutant kidneys Smooth muscle forms from condensed mesenchyme that underlies the urothelium in the ureter and the renal pelvis (McHugh, 1995)....
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...The metanephric mesenchyme, however, can adopt one of several fates, including epithelial renal vesicles, stroma or smooth muscle, in response to local signaling (Aufderheide et al., 1987; Herzlinger et al., 1992; Matsuno et al., 1984; McHugh, 1995; Saxen, 1987; Tacciuoli et al., 1975)....
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...Smooth muscle formation in the ureter has been reported to occur in cells immediately adjacent to the urothelium, a similar position to smooth muscle in the respiratory system (McHugh, 1995), which is also Shh dependent (Pepicelli et al....
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01 Jan 2016
TL;DR: The expression of several differentiation markers in normal human mammary gland myoepithelium and in certain stromal fibroblasts associated with breast carcinomas was studied by immunofluorescence microscopy of frozen sections as discussed by the authors.
Abstract: The expression of several differentiation markers in normal human mammary gland myoepithelium and in certain stromal fibroblasts ("myofibroblasts") associated with breast carcinomas was studied by immunofluorescence microscopy of frozen sections. Several antibodies to smooth muscle-specific proteins (smooth muscle c-actin, smooth mus- cle myosin heavy chains, calponin, a1-integrin, and high molecular weight caldesmon) and to epithelial-specific proteins (cytokeratins, E-cadherin, and desmoplakin) were used to show that myoepithelial cells concomitantly express epithelial and smooth muscle markers whereas adjacent luminal cells express only epithelial markers. The same antibodies were used to establish that stromal myofibroblasts exhibit smooth muscle phenotypic properties characterized by the expression of all the smooth muscle markers examined except for high molecular weight caldesmon. In addition, both myoepithelium and rnyo- fibroblasts show a significant degree of heterogeneity in smooth muscle protein expression. Thus, myoepithelial cells and stro- mal myofibroblasts are epithelial and mesenchymal cells, re- spectively, which coordinately express a set of smooth muscle markers while maintaining their specific original features. The dual nature of myoepithelial cells and the phenotypic transition of fibroblasts to myofibroblasts are examples of the plasticity of the differentiated cell phenotype.
276 citations
References
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TL;DR: The current state of knowledge of both vascular and visceral smooth muscle in cell and tissue culture and the variety of preparations used for different experimental purposes are described in this article, where the authors refer to organ culture of smooth muscle tissues only periodically.
Abstract: The current state of knowledge of both vascular and visceral smooth muscle in cell and tissue culture and the variety of preparations used for different experimental purposes are described. Organ culture of smooth muscle tissues is referred to only periodically.
1,460 citations
TL;DR: Different muscle cell types share a common myogenic differentiation program controlled by MEF2, which is determined by generating a loss-of-function of the single mef2 gene in Drosophila (D-mef2).
Abstract: Members of the myocyte enhancer binding factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, and serum response factor) box transcription factors are expressed in the skeletal, cardiac, and smooth muscle lineages of vertebrate and Drosophila embryos. These factors bind an adenine-thymidine-rich DNA sequence associated with muscle-specific genes. The function of MEF2 was determined by generating a loss-of-function of the single mef2 gene in Drosophila (D-mef2). In loss-of-function embryos, somatic, cardiac, and visceral muscle cells did not differentiate, but myoblasts were normally specified and positioned. These results demonstrate that different muscle cell types share a common myogenic differentiation program controlled by MEF2.
499 citations
TL;DR: The specific expression of the vascular smooth muscle alpha- actin gene marks the onset of differentiation of cardiac cells and represents the first demonstration of coexpression of both smooth muscle and striated alpha-actin genes within myogenic cells.
Abstract: The expression of cytoplasmic beta-actin and cardiac, skeletal, and smooth muscle alpha-actins during early avian cardiogenesis was analyzed by in situ hybridization with mRNA-specific single-stranded DNA probes. The cytoplasmic beta-actin gene was ubiquitously expressed in the early chicken embryo. In contrast, the alpha-actin genes were sequentially activated in avian cardiac tissue during the early stages of heart tube formation. The accumulation of large quantities of smooth muscle alpha-actin transcripts in epimyocardial cells preceded the expression of the sarcomeric alpha-actin genes. The accumulation of skeletal alpha-actin mRNAs in the developing heart lagged behind that of cardiac alpha-actin by several embryonic stages. At Hamburger-Hamilton stage 12, the smooth muscle alpha-actin gene was selectively down-regulated in the heart such that only the conus, which subsequently participates in the formation of the vascular trunks, continued to express this gene. This modulation in smooth muscle alpha-actin gene expression correlated with the beginning of coexpression of sarcomeric alpha-actin transcripts in the epimyocardium and the onset of circulation in the embryo. The specific expression of the vascular smooth muscle alpha-actin gene marks the onset of differentiation of cardiac cells and represents the first demonstration of coexpression of both smooth muscle and striated alpha-actin genes within myogenic cells.
306 citations
TL;DR: Myoepithelial cells and stromal myofibroblasts are epithelial and mesenchymal cells, respectively, which coordinately express a set of smooth muscle markers while maintaining their specific original features.
Abstract: The expression of several differentiation markers in normal human mammary gland myoepithelium and in certain stromal fibroblasts ("myofibroblasts") associated with breast carcinomas was studied by immunofluorescence microscopy of frozen sections. Several antibodies to smooth muscle-specific proteins (smooth muscle alpha-actin, smooth muscle myosin heavy chains, calponin, alpha 1-integrin, and high molecular weight caldesmon) and to epithelial-specific proteins (cytokeratins, E-cadherin, and desmoplakin) were used to show that myoepithelial cells concomitantly express epithelial and smooth muscle markers whereas adjacent luminal cells express only epithelial markers. The same antibodies were used to establish that stromal myofibroblasts exhibit smooth muscle phenotypic properties characterized by the expression of all the smooth muscle markers examined except for high molecular weight caldesmon. In addition, both myoepithelium and myofibroblasts show a significant degree of heterogeneity in smooth muscle protein expression. Thus, myoepithelial cells and stromal myofibroblasts are epithelial and mesenchymal cells, respectively, which coordinately express a set of smooth muscle markers while maintaining their specific original features. The dual nature of myoepithelial cells and the phenotypic transition of fibroblasts to myofibroblasts are examples of the plasticity of the differentiated cell phenotype.
286 citations
01 Jan 2016
TL;DR: The expression of several differentiation markers in normal human mammary gland myoepithelium and in certain stromal fibroblasts associated with breast carcinomas was studied by immunofluorescence microscopy of frozen sections as discussed by the authors.
Abstract: The expression of several differentiation markers in normal human mammary gland myoepithelium and in certain stromal fibroblasts ("myofibroblasts") associated with breast carcinomas was studied by immunofluorescence microscopy of frozen sections. Several antibodies to smooth muscle-specific proteins (smooth muscle c-actin, smooth mus- cle myosin heavy chains, calponin, a1-integrin, and high molecular weight caldesmon) and to epithelial-specific proteins (cytokeratins, E-cadherin, and desmoplakin) were used to show that myoepithelial cells concomitantly express epithelial and smooth muscle markers whereas adjacent luminal cells express only epithelial markers. The same antibodies were used to establish that stromal myofibroblasts exhibit smooth muscle phenotypic properties characterized by the expression of all the smooth muscle markers examined except for high molecular weight caldesmon. In addition, both myoepithelium and rnyo- fibroblasts show a significant degree of heterogeneity in smooth muscle protein expression. Thus, myoepithelial cells and stro- mal myofibroblasts are epithelial and mesenchymal cells, re- spectively, which coordinately express a set of smooth muscle markers while maintaining their specific original features. The dual nature of myoepithelial cells and the phenotypic transition of fibroblasts to myofibroblasts are examples of the plasticity of the differentiated cell phenotype.
276 citations