Pax3

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is most commonly inherited in an autosomal dominant pattern and caused by the abnormal expression of DUX4 in skeletal muscle. The DUX4 transcription factor has DNA binding domains similar to several paired class homeotic transcription factors, but only myogenic factors PAX3 and PAX7 rescue cell viability when co-expressed with DUX4 in mouse myoblasts. This observation suggests competition for DNA binding sites in satellite cells might limit muscle repair and may be one aspect of DUX4-associated myotoxicity...

Transcription factors are key orchestrators of the emergence of neuronal diversity within the developing spinal cord. As such, the two paralogous proteins Pax3 and Pax7 regulate the specification of progenitor cells within the intermediate neural tube, by defining a neat segregation between those fated to form motor circuits and those involved in the integration of sensory inputs. To attain insights into the molecular means by which they control this process, we have performed detailed phenotypic analyses of the intermediate spinal interneurons (IN), namely the dI6, V0D, V0VCG and V1 populations in compound null mutants for Pax3 and Pax7...

BACKGROUND: The organisation of vertebrate genomes into topologically associating domains (TADs) is believed to facilitate the regulation of the genes located within them. A remaining question is whether TAD organisation is achieved through the interactions of the regulatory elements within them or if these interactions are favoured by the pre-existence of TADs. If the latter is true, the fusion of two independent TADs should result in the rewiring of the transcriptional landscape and the generation of ectopic contacts...

Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...

Skeletal muscle in vertebrates is formed by two major routes, as illustrated by the mouse embryo. Somites give rise to myogenic progenitors that form all of the muscles of the trunk and limbs. The behavior of these cells and their entry into the myogenic program is controlled by gene regulatory networks, where paired box gene 3 (Pax3) plays a predominant role. Head and some neck muscles do not derive from somites, but mainly form from mesoderm in the pharyngeal region. Entry into the myogenic program also depends on the myogenic determination factor (MyoD) family of genes, but Pax3 is not expressed in these myogenic progenitors, where different gene regulatory networks function, with T-box factor 1 (Tbx1) and paired-like homeodomain factor 2 (Pitx2) as key upstream genes...

Binge eating (BE) is a common aberrant form of eating behavior, characterized by overconsumption of food in a brief period of time. Recurrent episodes of BE constitute the BE disorder, which mostly affects females and is associated with early-life adversities. Here, we show that corticotropin releasing factor (CRF)-induced prenatal stress (PNS) in late gestation predisposes female offspring to BE-like behavior that coincides with hypomethylation of hypothalamic miR-1a and downstream dysregulation of the melanocortin system through Pax7/Pax3...

The aim was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the Vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 weeks of NMES were allowed to proliferate to provide myogenic populations of adult stem cells (myogenic precursor cells; MPCs). These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca(2+) concentrations, and their expression of myogenic regulatory factors (PAX3, PAX7, MYF5, MYOD, MYOG) and microRNAs (miR-1, miR-133a/b, miR-206)...

PAX binding protein 1 (PAXBP1) is an adaptor protein linking the transcription factor PAX3 and PAX7 to the histone methylation machinery. PAXBP1 is a nuclear protein and its high expression is known in brain cerebellar hemisphere and cerebellum. Moreover, it is also found in abundance in muscle precursor cells that are involved in myogenesis and skeletal muscles formation. Whole genome SNP genotyping and exome sequencing in a family with distinct syndrome of global developmental delay and hypotonia mapped the disease locus to the chromosome 21q22...

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD). Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle...

Despite its modest capacity for regeneration, peripheral nervous system injury often results in significant long-term disability. Supplementing peripheral nervous system injury with autologous Schwann cells (SCs) may serve to rejuvenate the postinjury environment to enhance regeneration and ultimately improve functional outcomes. However, human nerve-derived SC (hN-SC) collection procedures require invasive surgical resection. Here, we describe the characterization of SCs from adult human skin (hSk-SCs) of four male donors ranging between 27 and 46 years old...

OBJECTIVE: To examine and expand the genetic spectrum of Waardenburg syndrome type 1 (WS1). METHODS: Clinical features related to Waardenburg syndrome (WS) were examined in a five-year old patient. Mutation analysis of genes related to WS was performed in the proband and her parents. Molecular modeling of EDNRB and the p.R319W mutant was conducted to predict the pathogenicity of the mutation. RESULTS: The proband showed sensorineural hearing loss, heterochromia iridis, and dystopia canthorum, fulfilling the clinical criteria of WS1...

Alveolar rhabdomyosarcoma is a life-threatening myogenic cancer of children and adolescent young adults, driven primarily by the chimeric transcription factor PAX3-FOXO1 (P3F). The mechanisms by which P3F dysregulates chromatin are unknown. We find P3F reprograms the cis-regulatory landscape by inducing (de novo) super enhancers (SEs). P3F uses SEs to setup auto-regulatory loops in collaboration with master transcription factors MYOG, MYOD and MYCN. This myogenic SE circuitry is consistent across cell lines and primary tumors...

White spotting phenotypes in horses can range in severity from the common white markings up to completely white horses. EDNRB, KIT, MITF, PAX3 and TRPM1 represent known candidate genes for such phenotypes in horses. For the present study, we re-investigated a large horse family segregating a variable white spotting phenotype, for which conventional Sanger sequencing of the candidate genes' individual exons had failed to reveal the causative variant. We obtained whole genome sequence data from an affected horse and specifically searched for structural variants in the known candidate genes...

The tongue is one of the major structures involved in human food intake and speech. Tongue malformations such as aglossia, microglossia, and ankyloglossia are congenital birth defects, greatly affecting individuals' quality of life. However, the molecular basis of the tissue-tissue interactions that ensure tissue morphogenesis to form a functional tongue remains largely unknown. Here we show that Shh(Cre) -mediated epithelial deletion of Wntless (Wls), the key regulator for intracellular Wnt trafficking, leads to lingual hypoplasia in mice...

Mice with dominant white spotting occurred spontaneously in the C3.NSY-(D11Mit74-D11Mit229) strain. Linkage analysis indicated that the locus for white spotting was located in the vicinity of the Pax3 gene on chromosome 1. Crosses of white-spotted mice showed that homozygosity for the mutation caused tail and limb abnormalities and embryonic lethality as a result of exencephaly; these phenotypes were analogous to those found in other Pax3 mutants. Sequence analysis identified a missense point mutation (c.101G>A) in exon 2 of Pax3 that resulted in a methionine to isoleucine conversion at amino acid 62 of the PAX3 protein...

Fusion of genes in tumours can have oncogenic roles in reprogramming cells through overexpression of oncogenes or the production of novel fusion proteins. A fundamental question in cancer biology is what genetic events are critical for initiation and whether these are also required for cancer progression. In recent work published in The Journal of Pathology, dependency on a fusion protein was addressed using a model of alveolar rhabdomyosarcomas - a sarcoma subtype with frequent fusion of PAX3 and FOXO1 genes that is associated with poor outcome...

Devil facial tumour disease (DFTD) has decimated wild populations of Tasmanian devils (Sarcophilus harrisii) due to its ability to avoid immune detection and pass from host to host by biting. A small number of devils have been observed to spontaneously recover from the disease which is otherwise fatal. We have sequenced the genomes of these rare cases and compared them to the genomes of devils who succumbed to the disease. Genome-wide association, based on this limited sampling, highlighted two key genomic regions potentially associated with ability to survive DFTD...

In a previous study, we reported on a quantitative transcriptomic method which confirmed the temporal transcription of developmental fast skeletal muscle myosin heavy chain (fsMyHC) embryonic isoforms in the embryonic Pectoralis major (PM) of the Single Comb White Leghorn (SCWL). The objective of the current study was to further investigate the transcriptional events underlying embryonic PM growth in the SCWL and a genotype exhibiting partial muscular dystrophy, the Low Score Normal (LSN). We hypothesized that within the SCWL and LSN embryos, there would be differences in the temporal transcription of the fsMyHC isoforms and other myogenic regulatory genes...

While the typical Arabian camel is characterized by a single colored coat, there are rare populations with white spotting patterns. White spotting coat patterns are found in virtually all domesticated species, but are rare in wild species. Theories suggest that white spotting is linked to the domestication process, and is occasionally associated with health disorders. Though mutations have been found in a diverse array of species, fewer than 30 genes have been associated with spotting patterns, thus providing a key set of candidate genes for the Arabian camel...

Satellite cells, also known as muscle stem cells, are responsible for skeletal muscle growth and repair in mammals. Pax7 and Pax3 transcription factors are established satellite cell markers required for muscle development and regeneration, and there is great interest in identifying additional factors that regulate satellite cell proliferation, differentiation, and/or skeletal muscle regeneration. Due to the powerful regenerative capacity of many zebrafish tissues, even in adults, we are exploring the regenerative potential of adult zebrafish skeletal muscle...