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      The Characterisation of Pax3 Expressant Cells in Adult Peripheral Nerve

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      PLoS ONE
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          Abstract

          Pax3 has numerous integral functions in embryonic tissue morphogenesis and knowledge of its complex function in cells of adult tissue continues to unfold. Across a variety of adult tissue lineages, the role of Pax3 is principally linked to maintenance of the tissue’s resident stem/progenitor cell population. In adult peripheral nerves, Pax3 is reported to be expressed in nonmyelinating Schwann cells, however, little is known about the purpose of this expression. Based on the evidence of the role of Pax3 in other adult tissue stem and progenitor cells, it was hypothesised that the cells in adult peripheral nerve that express Pax3 may be peripheral glioblasts. Here, methods have been developed for identification and visualisation of Pax3 expressant cells in normal 60 day old mouse peripheral nerve that allowed morphological and phenotypic distinctions to be made between Pax3 expressing cells and other nonmyelinating Schwann cells. The distinctions described provide compelling support for a resident glioblast population in adult mouse peripheral nerve.

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          Most cited references72

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          Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells.

          The pluripotency of embryonic stem (ES) cells is thought to be maintained by a few key transcription factors, including Oct3/4 and Sox2. The function of Oct3/4 in ES cells has been extensively characterized, but that of Sox2 has yet to be determined. Sox2 can act synergistically with Oct3/4 in vitro to activate Oct-Sox enhancers, which regulate the expression of pluripotent stem cell-specific genes, including Nanog, Oct3/4 and Sox2 itself. These findings suggest that Sox2 is required by ES cells for its Oct-Sox enhancer activity. Using inducible Sox2-null mouse ES cells, we show that Sox2 is dispensable for the activation of these Oct-Sox enhancers. In contrast, we demonstrate that Sox2 is necessary for regulating multiple transcription factors that affect Oct3/4 expression and that the forced expression of Oct3/4 rescues the pluripotency of Sox2-null ES cells. These results indicate that the essential function of Sox2 is to stabilize ES cells in a pluripotent state by maintaining the requisite level of Oct3/4 expression.
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            A Pax3/Pax7-dependent population of skeletal muscle progenitor cells.

            During vertebrate development, successive phases of embryonic and fetal myogenesis lead to the formation and growth of skeletal muscles. Although the origin and molecular regulation of the earliest embryonic muscle cells is well understood, less is known about later stages of myogenesis. We have identified a new cell population that expresses the transcription factors Pax3 and Pax7 (paired box proteins 3 and 7) but no skeletal-muscle-specific markers. These cells are maintained as a proliferating population in embryonic and fetal muscles of the trunk and limbs throughout development. Using a stable green fluorescent protein (GFP) reporter targeted to Pax3, we demonstrate that they constitute resident muscle progenitor cells that subsequently become myogenic and form skeletal muscle. Late in fetal development, these cells adopt a satellite cell position characteristic of progenitor cells in postnatal muscle. In the absence of both Pax3 and Pax7, further muscle development is arrested and only the early embryonic muscle of the myotome forms. Cells failing to express Pax3 or Pax7 die or assume a non-myogenic fate. We conclude that this resident Pax3/Pax7-dependent progenitor cell population constitutes a source of myogenic cells of prime importance for skeletal muscle formation, a finding also of potential value in the context of cell therapy for muscle disease.
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              Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells

              The growth and repair of skeletal muscle after birth depends on satellite cells that are characterized by the expression of Pax7. We show that Pax3, the paralogue of Pax7, is also present in both quiescent and activated satellite cells in many skeletal muscles. Dominant-negative forms of both Pax3 and -7 repress MyoD, but do not interfere with the expression of the other myogenic determination factor, Myf5, which, together with Pax3/7, regulates the myogenic differentiation of these cells. In Pax7 mutants, satellite cells are progressively lost in both Pax3-expressing and -nonexpressing muscles. We show that this is caused by satellite cell death, with effects on the cell cycle. Manipulation of the dominant-negative forms of these factors in satellite cell cultures demonstrates that Pax3 cannot replace the antiapoptotic function of Pax7. 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.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                19 March 2013
                : 8
                : 3
                : e59184
                Affiliations
                [1 ]School of Medical Science, Edith Cowan University, Joondalup, Western Australia, Australia
                [2 ]School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia, Australia
                University of Edinburgh, United Kingdom
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MRZ JAB. Performed the experiments: MRZ JAB. Analyzed the data: MRZ JAB. Contributed reagents/materials/analysis tools: MRZ JAB. Wrote the paper: MRZ JAB.

                Article
                PONE-D-12-37826
                10.1371/journal.pone.0059184
                3602598
                23527126
                98e1a4b4-e582-46e3-a0c1-7b0624d93d89
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 November 2012
                : 12 February 2013
                Page count
                Pages: 10
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Neurological System
                Nerve Tissue
                Peripheral Nervous System
                Developmental Biology
                Stem Cells
                Adult Stem Cells
                Cell Differentiation
                Genetics
                Histology
                Model Organisms
                Animal Models
                Mouse
                Molecular Cell Biology
                Cellular Types
                Stem Cells
                Adult Stem Cells
                Medicine
                Anatomy and Physiology
                Neurological System
                Nerve Tissue
                Peripheral Nervous System
                Neurology

                Uncategorized
                Uncategorized

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