Collins, CA;
Gnocchi, VF;
White, RB;
Boldrin, L;
Perez-Ruiz, A;
Relaix, F;
Morgan, JE;
(2009)
Integrated Functions of Pax3 and Pax7 in the Regulation of Proliferation, Cell Size and Myogenic Differentiation.
PLOS ONE
, 4
(2)
, Article e4475. 10.1371/journal.pone.0004475.
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Abstract
Pax3 and Pax7 are paired-box transcription factors with roles in developmental and adult regenerative myogenesis. Pax3 and Pax7 are expressed by postnatal satellite cells or their progeny but are down regulated during myogenic differentiation. We now show that constitutive expression of Pax3 or Pax7 in either satellite cells or C2C12 myoblasts results in an increased proliferative rate and decreased cell size. Conversely, expression of dominant-negative constructs leads to slowing of cell division, a dramatic increase in cell size and altered morphology. Similarly to the effects of Pax7, retroviral expression of Pax3 increases levels of Myf5 mRNA and MyoD protein, but does not result in sustained inhibition of myogenic differentiation. However, expression of Pax3 or Pax7 dominant-negative constructs inhibits expression of Myf5, MyoD and myogenin, and prevents differentiation from proceeding. In fibroblasts, expression of Pax3 or Pax7, or dominant-negative inhibition of these factors, reproduce the effects on cell size, morphology and proliferation seen in myoblasts. Our results show that in muscle progenitor cells, Pax3 and Pax7 function to maintain expression of myogenic regulatory factors, and promote population expansion, but are also required for myogenic differentiation to proceed.
| Type: | Article |
|---|---|
| Title: | Integrated Functions of Pax3 and Pax7 in the Regulation of Proliferation, Cell Size and Myogenic Differentiation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0004475 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0004475 |
| Language: | English |
| Additional information: | © 2009 Collins et al. 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. C.A.C. and L.B. were funded by the Muscular Dystrophy Campaign (RA3/711). V.F.G. received support from the Medical Research Council (grant number G0700307). R.B.W. was funded by the Muscular Dystrophy Campaign (RA3/762), and currently, by The Wellcome Trust (085137), while A.P.R. was funded by a Fundacion Ramon Areces post-doctoral fellowship. F.R. is funded by the INSERM Avenir program, UPMC, Institut de Myologie, AFM and is a member of the EU 6th framework programme MYORES network of excellence. J.E.M. was funded by an MRC Joint Collaborative Career Development Award in Stem Cell Research and is currently funded by a Wellcome Trust university award. The laboratory of P.S.Z. is also supported by the Association of International Cancer Research and the MYORES Network of Excellence contract 511978 from the European Commission 6th Framework Programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/82388 |
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