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Abstract
Striated muscles that enable mouth opening and swallowing during feeding are essential for efficient energy acquisition, and are likely to have played a fundamental role in the success of early jawed vertebrates. The developmental origins and genetic requirements of these muscles are uncertain. Here, we determine by indelible lineage tracing in mouse that fibres of sternohyoid muscle (SHM), which is essential for mouth opening during feeding, and oesophageal striated muscle (OSM), which is crucial for voluntary swallowing, arise from Pax3-expressing somite cells. In vivo Kaede lineage tracing in zebrafish reveals the migratory route of cells from the anteriormost somites to OSM and SHM destinations. Expression of pax3b, a zebrafish duplicate of Pax3, is restricted to the hypaxial region of anterior somites that generate migratory muscle precursors (MMPs), suggesting that Pax3b plays a role in generating OSM and SHM. Indeed, loss of pax3b function led to defective MMP migration and OSM formation, disorganised SHM differentiation, and inefficient ingestion and swallowing of microspheres. Together, our data demonstrate Pax3-expressing somite cells as a source of OSM and SHM fibres, and highlight a conserved role of Pax3 genes in the genesis of these feeding muscles of vertebrates.
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Abstract
Skeletal muscle contains Pax7-expressing muscle stem or satellite cells, enabling muscle regeneration throughout most of adult life. Here, we demonstrate that induced inactivation of Pax7 in Pax7-expressing cells of adult mice leads to loss of muscle stem cells and reduced heterochromatin condensation in rare surviving satellite cells. Inactivation of Pax7 in Myf5-expressing cells revealed that the majority of adult muscle stem cells originate from myogenic lineages, which express the myogenic regulators Myf5 or MyoD. Likewise, the majority of muscle stem cells are replenished from Myf5-expressing myogenic cells during adult life, and inactivation of Pax7 in Myf5-expressing cells after muscle damage leads to a complete arrest of muscle regeneration. Finally, we demonstrate that a relatively small number of muscle stem cells are sufficient for efficient repair of skeletal muscles. We conclude that Pax7 acts at different levels in a nonhierarchical regulatory network controlling muscle-satellite-cell-mediated muscle regeneration.
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Abstract
The potential structures of platinum nitride with a chemical composition of PtN2 have been examined by utilizing a widely adopted evolutionary methodology for crystal structure prediction. Except reproducing the previously proposed phases, a Pmmm symmetric novel layer structure with a low formation enthalpy that is slightly lower than those of marcasite and CoSb2 structures but slightly higher than that of pyrite structure has also been identified. The elastic constants and the lattice dynamical calculations show that this layer-structured PtN2 is mechanically and dynamically stable. The calculated band structures suggest this new phase together with the simple tetragonal phase are metallic, while other phases are insulators. In addition, it has been found by the phonon spectrum calculations that the fluorite structure is dynamically unstable, although it is mechanically stable as suggested by calculated elastic constants.
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Abstract
Elemental silicon has a large impact on the economy of the modem world and is of fundamental importance in the technological field, particularly in solar cell industry. The great demand of society for new clean energy and the shortcomings of the current silicon solar cells are calling for new materials that can make full use of the solar power. In this paper, six metastable allotropes of silicon with direct or quasidirect band gaps of 0.39-1.25 eV are predicted by ab initio calculations at ambient pressure. Five of them possess band gaps within the optimal range for high converting efficiency from solar energy to electric power and also have better optical properties than the Si-I phase. These Si structures with different band gaps could be applied to multiple p-n junction photovoltaic modules.
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Abstract
We report the generation of five mouse strains with the tamoxifen-inducible Cre (Cre-ERT2; CE) gene cassette knocked into the endogenous loci of Pax3, Myod1, Myog, Myf6, and Myl1, collectively as a resource for the skeletal muscle research community. We characterized these CE strains using the Cre reporter mice, R26R(LacZ), during embryogenesis and show that they direct tightly controlled tamoxifen-inducible reporter expression within the expected cell lineage determined by each myogenic gene. We also examined a few selected adult skeletal muscle groups for tamoxifen-inducible reporter expression. None of these new CE alleles direct reporter expression in the cardiac muscle. All these alleles follow the same knock-in strategy by replacing the first exon of each gene with the CE cassette, rendering them null alleles of the endogenous gene. Advantages and disadvantages of this design are discussed. Although we describe potential immediate use of these strains, their utility likely extends beyond foreseeable questions in skeletal muscle biology. (C) 2014 Wiley Periodicals, Inc.
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Abstract
During muscle regeneration, the transcription factor Pax7 stimulates the differentiation of satellite cells (SCs) toward the muscle lineage but restricts adipogenesis. Here, we identify HDAC4 as a regulator of Pax7-dependent muscle regeneration. In HDAC4-deficient SCs, the expression of Pax7 and its target genes is reduced. We identify HDAC4-regulated Lix1 as a Pax7 target gene required for SC proliferation. HDAC4 inactivation leads to defective SC proliferation, muscle regeneration, and aberrant lipid accumulation. Further, expression of the brown adipose master regulator Prdm16 and its inhibitory microRNA-133 are also deregulated. Thus, HDAC4 is a novel regulator of Pax7-dependent SC proliferation and potentially fate determination in regenerating muscle.
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Abstract
The single-minded (sim) gene encodes a transcriptional regulator that functions as a key determinant of central nervous system (CNS) midline development in Drosophila, We report here the identification of two murine homologs of sim, Sim1 and Sim2 whose products show a high degree of sequence conservation with Drosophila SIM in their amino-terminal halves, with each containing a basic helix-loop-helix domain as well as a PAS domain, Sim1 maps to the proximal region of mouse chromosome 10, whereas Sim2 maps to a portion of the distal end of chromosome 16 that is syntenic to the Down syndrome critical region of human chromosome 21., Recent exon-trapping studies have identified in the critical region several exons of a human sim homolog which appears to be the homolog of murine Sim2; this has led to the hypothesis that increased dosage of this sim homolog in cases of trisomy 21 might be a causal factor in the pathogenesis of Down syndrome, We have examined the expression patterns of the Sim genes during embryogenesis. Both genes are expressed in dynamic and selective fashion in specific neuromeric compartments of the developing forebrain, and the expression pattern of Sima provides evidence for early regionalization of the diencephalon prior to any overt morphological differentiation in this region, Outside the CNS, Sim1 is expressed in mesodermal and endodermal tissues, including developing somites, mesonephric duct, and foregut, Sim2 is expressed in facial and trunk cartilage, as well as trunk muscles. Both murine Sim genes are also expressed in the developing kidney, Our data suggest that the Sim genes play roles in directing the regionalization of tissues where they are expressed, Moreover, the expression pattern documented for Sima may provide insights into its potential roles in Down syndrome.
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Abstract
WNT signaling plays a major role in patterning the dermomyotome of the somitic mesoderm. However, knowledge of downstream target genes and their regulation is limited. To identify new genes involved in the development and early patterning of the somite, we performed a comparison of gene expression by microarray between the presomitic mesoderm and the 5 most recently formed somites of the mouse at embryonic day 9.5. We identified 207 genes upregulated and 120 genes downregulated in somite formation. Expression analysis and functional categorization of these genes demonstrate this to be a diverse pool that provides a valuable resource for studying somite development. Thus far, we have found three genes expressed in the dermomyotome of the early somite. Consistent with their expression patterns, these genes are transcriptional targets of WNT signals, but display differential activation by different WNTs. We further demonstrate that I of these genes, Troy, is a direct target of canonical WNT signaling, while the other 2 genes, Selp and Arl4, are not. Thus, our microarray study using microdissected tissues not only provides global information on gene expression during somite development, it also provides novel targets to study the inductive signaling pathways that direct somite patterning. (C) 2003 Elsevier Science (USA). All rights reserved.
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