TitleRegulation of motility of myogenic cells in filling limb muscle anlagen by Pitx2.
Publication TypeJournal Article
Year of Publication2012
AuthorsCampbell AL, Shih H-P, Xu J, Gross MK, Kioussi C
JournalPLoS One
Date Published2012
KeywordsAnimals, Cell Differentiation, Cell Movement, Cell Polarity, Cell Size, Embryo, Mammalian, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Homeodomain Proteins, Limb Buds, Mice, Mice, Transgenic, Muscle Development, Muscle, Skeletal, Signal Transduction, Time-Lapse Imaging, Transcription Factors

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(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.

Alternate JournalPLoS ONE
PubMed ID22558231
PubMed Central IDPMC3338778
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
R01 AR054406 / AR / NIAMS NIH HHS / United States
AR054406 / AR / NIAMS NIH HHS / United States
P30ES000210 / ES / NIEHS NIH HHS / United States