Kumar, A;
Velloso, CP;
Imokawa, Y;
Brockes, JP;
(2004)
The regenerative plasticity of isolated urodele myofibers and its dependence on Msx1.
PLoS Biology
, 2
(8)
, Article e218. 10.1371/journal.pbio.0020218.
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Abstract
The conversion of multinucleate postmitotic muscle fibers to dividing mononucleate progeny cells (cellularisation)occurs during limb regeneration in salamanders, but the cellular events and molecular regulation underlying this remarkable process are not understood. The homeobox gene Msx1 has been studied as an antagonist of muscle differentiation, and its expression in cultured mouse myotubes induces about 5% of the cells to undergo cellularisation and viable fragmentation, but its relevance for the endogenous programme of salamander regeneration is unknown. We dissociated muscle fibers from the limb of larval salamanders and plated them in culture. Most of the fibers were activated by dissociation to mobilise their nuclei and undergo cellularisation or breakage into viable multinucleate fragments. This was followed by microinjection of a lineage tracer into single fibers and analysis of the labelled progeny cells, as well as by time-lapse microscopy. The fibers showing morphological plasticity selectively expressed Msx1 mRNA and protein. The uptake of morpholino antisense oligonucleoticles directed to Msx1 led to a specific decrease in expression of Msx1 protein in myonuclei and marked inhibition of cellularisation and fragmentation. Myofibers of the salamander respond to dissociation by activation of an endogenous programme of cellularisation and fragmentation. Lineage tracing demonstrates that cycling mononucleate progeny cells are derived from a single myofiber. The induction of Msx1 expression is required to activate this programme. Our understanding of the regulation of plasticity in postmitotic salamander cells should inform strategies to promote regeneration in other contexts.
| Type: | Article |
|---|---|
| Title: | The regenerative plasticity of isolated urodele myofibers and its dependence on Msx1 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pbio.0020218 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pbio.0020218 |
| Additional information: | © 2004 Kumar 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 work is properly cited. |
| Keywords: | VERTEBRATE LENS REGENERATION, GAP JUNCTIONAL COMMUNICATION, S-PHASE REENTRY, LIMB REGENERATION, CELL-CYCLE, EPITHELIAL-CELLS, SATELLITE CELLS, HOMEOBOX GENES, MUSCLE-FIBERS, NEWT MYOTUBES |
| 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 Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/130890 |
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