Margaret Buckingham

..The myogenic identity of precursor cells in the adult depends on Pax7, the orthologue of Pax3 which is required for early myogenesis; this finding is of major importance for muscle regeneration and the active field of stem cell research...

..The latter include the smooth muscle cells of the dorsal aorta that share a common clonal origin with the skeletal muscle of the myotome, thus illustrating the initial multipotency of Pax3 expressing cells...

..Pax3/7 lies genetically upstream of both MyoD and Myf5, which determine the skeletal muscle fate of these cells. To cite this article: M. Buckingham, C. R. Biologies 330 (2007)...

..This raises the question of the co-ordination between these events and the community effect which orchestrates myogenesis...

..It also has an important influence on the interpretation of mutant phenotypes in the mouse, with consequences for the classification and prognosis of human congenital heart defects...

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..Finally, we consider the molecular mechanisms that underlie the function of Pax transcription factors, including the cofactors and regulatory networks with which they interact...

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..New approaches that permit the grafting of purified satellite cells demonstrate their capacity for efficient muscle repair and for self-renewal. Regeneration in amphibians is now also shown to involve Pax-positive progenitor cells...

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..We revise the epistatic relationship of the MRFs, in which both Myf5 and Mrf4 act upstream of Myod to direct embryonic multipotent cells into the myogenic lineage...

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..These findings underline the importance of cell survival in controlling the stem cell populations of adult tissues and demonstrate a role for upstream factors in this context...

..Few Pax3 target genes have been identified. Identifying genes that lie genetically downstream of Pax3 is therefore an important endeavour in elucidating the myogenic gene regulatory network...

..We therefore conclude that miR-27b regulates Pax3 protein levels and this down-regulation ensures rapid and robust entry into the myogenic differentiation program...

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..These observations are discussed with respect to the origin and function of Pax3-expressing cells in blood vessels, and more general questions of cell fate determination and adult cell plasticity and reprogramming...

..Six homeoproteins, which also directly regulate the myogenic differentiation gene Myogenin and lie genetically upstream of Pax3, thus control hypaxial myogenesis at multiple levels...

..These results reveal a novel genetic network, comprising a Pax3/Dmrt2/Myf5 regulatory cascade that operates in stem cells of the epaxial dermomyotome to initiate skeletal muscle formation...

..The Wnt-beta catenin signalling pathway is also implicated. Finally we show that post-transcriptional regulation of Myf5 gene expression involves miRNA repression acting through the Myf5-3'UTR...

..Such cells, grafted into muscles of mdx nu/nu mice, contributed both to fiber repair and to the muscle satellite cell compartment. Expansion of these cells in culture before engraftment reduced their regenerative capacity...

..We therefore propose a model in which posttranscriptional mechanisms hold quiescent stem cells poised to enter a tissue-specific differentiation program...

..These observations identify A17 as a sequence that targets sites of myogenesis in vivo and raise questions about the mutually exclusive modes of expression and possible promoter/enhancer interactions at the Mrf4-Myf5 locus...

..The Mlc3f-nlacZ-2 line, which marks the right atrium, allowed us to determine the time window during which left-right signaling confers left-right atrial identity...

..In keeping with this, we demonstrate that metalloproteinase function is required for efficient regeneration in vivo...

..Therefore, Pax-3 and Myf-5 define two distinct myogenic pathways, and MyoD acts genetically downstream of these genes for myogenesis in the body. This genetic hierarchy does not appear to operate for head muscle formation...

..Mutation of the Pax3 site abolishes all expression controlled by the 145-bp sequence in transgenic mouse embryos. We conclude that Pax3 directly regulates Myf5 in the hypaxial somite and its derivatives...

..Our findings provide a paradigm for transcriptional mechanisms that underlie the changes in regulatory networks during the transition from progenitor state to that of the differentiated tissue...

..Integration of results from genetic tracing into the lineage tree adds a further temporal dimension to this reconstruction of the history of venous myocardium and the arterial pole...

..Our result suggests that Pax3/7 and Pax2/5/8 functions evolved independently after duplication of the ancestral progenitor Pax genes...

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..This provides insight into how cell fate choices are orchestrated by these lineage genes in the dermomyotome...

..This gain-of-function allele provides a new approach to the molecular and cellular analysis of the role of Pax3 and of its target genes in vivo...

..In its absence, muscle progenitors, having activated myf-5, remain multipotent and differentiate into other somitic derivatives according to their local environment...

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..These results suggest that the myf-5 gene is not activated in only a subset of muscle cells and are consistent with the results on the MyoD knockout mice...

..Such regulatory heterogeneity may underlie the observed restriction of myopathies to particular muscle subgroups...

..However, recent studies have revealed a role for the myocardium in the formation of both the arterial and venous poles of the heart...

..Further insights into myogenic populations that contribute to trunk and limb development at different stages are summarized and the distinct regulatory networks that underlie the formation of head muscles are discussed...

..These results provide new insight into the Pax-initiated regulatory network that modulates stem cell maintenance versus tissue differentiation...

..Knowledge about the origin and genetic regulation of cells that contribute to the heart and associated vasculature is important for the diagnosis and treatment of congenital heart malformations...

..We discuss the unexpected finding which was made with the myf-5/nlsLacZ mice, that myf-5 is also expressed in the central nervous system...

..This phenomenon may be widespread and it remains to be seen how many other potentially potent regulatory genes, in addition to Myf5, when activated do not accumulate protein at inappropriate sites in the embryo...

..Mice lacking myogenin have little skeletal muscle as fibres fail to differentiate. Lack of both MyoD and myf-5 results in no skeletal muscle and apparently no myoblasts, suggesting that these factors act earlier in muscle development...

..Right and left ventricular lineages appear to segregate early, in agreement with the existence of two populations of cardiac precursors, the so-called primary (or posterior) and secondary (or anterior) heart fields...

..Mutations within the CArG box distinguish between the binding of this complex and binding of SRF; only SRF binding is directly involved in the specific regulation of the MLC1A gene in skeletal muscle cell lines...

..These genes might be implicated in patterning events at these sites through the activation of other genes directly involved in the definition of positional information, such as Hox genes...

..These results are discussed in terms of the paraxial mesoderm contribution to the aorta and of the mesoangioblast stem cells that derive from it...

..The time and place of myf-5 expression are consistent with a role in the early events of myogenic differentiation, possibly during determination of the myogenic lineage...

..These results demonstrate the importance of this novel complex in the transcriptional regulation of the cardiac actin gene and suggest a potential role in chromatin remodeling associated with muscle gene activation...

..We show here that transgene-directed expression of the MLC3F promoter reflects low level expression of endogenous MLC3F transcripts in the mouse heart...

..2010) shows that the presence of functional dystrophin is required for NO-dependent nitrosylation of the HDAC2 repressor and subsequent activation of a group of microRNAs required for muscle function...

..Il6 did not recombine with either Hm or Hx and, therefore, provides a point of access for the analysis of these mutations at the molecular level...

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..In this review we will summarize the current knowledge on the regulatory circuits that lead to the establishment of skeletal muscle in these different anatomical regions...

..This and other aspects of Pax3/7 function in regulating the behavior of skeletal muscle stem cells are discussed...

..The pronounced accumulation and regional localization of Hox-7 transcripts in mandibular and limb processes point to a specific morphogenetic role for this mouse homeobox gene...

..This dynamic pattern of changes in the myosin phenotype in the prenatal mouse heart suggests that there are different regulatory mechanisms for cell-specific expression of myosin isoforms during cardiac development...

..The data presented are the first detailed study of myosin gene expression at these early stages of skeletal muscle development...

..When a quail ridge is grafted over nonexpressing mesoderm, a new site of expression is induced. Therefore, Hox-7 and Hox-8 depend on a functional ridge for their continued expression in the limb bud and can be induced by it...

..7-kb TaqI fragment corresponds indeed to a functional gene...