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Regulation of Motility of Myogenic Cells in Filling Limb Muscle Anlagen by Pitx2

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dc.creator Campbell, Adam L.
dc.creator Shih, Hung-Ping
dc.creator Xu, Jun
dc.creator Gross, Michael K.
dc.creator Kioussi, Chrissa
dc.date.accessioned 2012-08-08T18:27:49Z
dc.date.available 2012-08-08T18:27:49Z
dc.date.issued 2012-04-27
dc.identifier.citation Campbell AL, Shih H-P, Xu J, Gross MK, Kioussi C (2012) Regulation of Motility of Myogenic Cells in Filling Limb Muscle Anlagen by Pitx2. PLoS ONE 7(4): e35822. doi:10.1371/journal.pone.0035822 en_US
dc.identifier.uri http://hdl.handle.net/1957/32032
dc.description This is the publisher’s final pdf. The published article is copyrighted by PLoS and can be found at: http://www.plosone.org/home.action. en_US
dc.description.abstract Cells of the ventrolateral dermomyotome delaminate and migrate into the limb buds where they give rise to all muscles of the limbs. The migratory cells proliferate and form myoblasts, which withdraw from the cell cycle to become terminally differentiated myocytes. The myogenic lineage colonizes pre-patterned regions to form muscle anlagen as muscle fibers are assembled. The regulatory mechanisms that control the later steps of this myogenic program are not well understood. The homeodomain transcription factor Pitx2 is expressed specifically in the muscle lineage from the migration of precursors to adult muscle. Ablation of Pitx2 results in distortion, rather than loss, of limb muscle anlagen, suggesting that its function becomes critical during the colonization of, and/or fiber assembly in, the anlagen. Microarrays were used to identify changes in gene expression in flow-sorted migratory muscle precursors, labeled by Lbx1[superscript EGFP/+], which resulted from the loss of Pitx2. Very few genes showed changes in expression. Many small-fold, yet significant, changes were observed in genes encoding cytoskeletal and adhesion proteins which play a role in cell motility. Myogenic cells from genetically-tagged mice were cultured and subjected to live cell-tracking analysis using time-lapse imaging. Myogenic cells lacking Pitx2 were smaller, more symmetrical, and had more actin bundling. They also migrated about half of the total distance and velocity. Decreased motility may prevent myogenic cells from filling pre-patterned regions of the limb bud in a timely manner. Altered shape may prevent proper assembly of higher-order fibers within anlagen. Pitx2 therefore appears to regulate muscle anlagen development by appropriately balancing expression of cytoskeletal and adhesion molecules. en_US
dc.description.sponsorship This work was supported by National Institutes of Health-National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS) grant AR054406 to CK. en_US
dc.language.iso en_US en_US
dc.publisher PLoS en_US
dc.relation.ispartofseries PLoS ONE en_US
dc.relation.ispartofseries Vol. 7 no. 4 en_US
dc.subject Dependent protein kinase en_US
dc.subject Actin based motility en_US
dc.subject Precursor cells en_US
dc.subject Mouse embryo en_US
dc.subject Gene expression en_US
dc.subject Signal transduction en_US
dc.subject Binding protein en_US
dc.subject Skeletal muscle en_US
dc.subject C-met en_US
dc.title Regulation of Motility of Myogenic Cells in Filling Limb Muscle Anlagen by Pitx2 en_US
dc.type Article en_US
dc.identifier.doi 10.1371/journal.pone.0035822


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