Effects of retinoic acid signaling on extraocular muscle myogenic precursor cells in vitro

One major difference between limb and extraocular muscles (EOM) is the presence of an enriched population of Pitx2-positive myogenic precursor cells in EOM compared to limb muscle. We hypothesize that retinoic acid regulates Pitx2 expression in EOM myogenic precursor cells and that its effects would...

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Bibliographic Details
Published in:Experimental cell research 2017-12, Vol.361 (1), p.101-111
Main Authors: Hebert, Sadie L., Fitzpatrick, Krysta R., McConnell, Samantha A., Cucak, Anja, Yuan, Ching, McLoon, Linda K.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Cell Proliferation - drug effects
Cells, Cultured
Extraocular muscle
Homeobox Protein PITX2
Homeodomain Proteins - metabolism
In Vitro Techniques
Keratolytic Agents - pharmacology
Mice
Mice, Inbred C57BL
Muscle Development - drug effects
Muscle Development - physiology
Muscle stem cells
Muscle, Skeletal - cytology
Muscle, Skeletal - drug effects
Muscle, Skeletal - metabolism
Myoblasts - cytology
Myoblasts - drug effects
Myoblasts - metabolism
Oculomotor Muscles - cytology
Oculomotor Muscles - drug effects
Oculomotor Muscles - metabolism
PAX7 Transcription Factor - metabolism
Retinoic acid
Retinoic acid signaling
Retinoid X Receptors - metabolism
Transcription Factors - metabolism
Tretinoin - pharmacology
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Summary:One major difference between limb and extraocular muscles (EOM) is the presence of an enriched population of Pitx2-positive myogenic precursor cells in EOM compared to limb muscle. We hypothesize that retinoic acid regulates Pitx2 expression in EOM myogenic precursor cells and that its effects would differ in leg muscle. The two muscle groups expressed differential retinoic acid receptor (RAR) and retinoid X receptor (RXR) levels. RXR co-localized with the Pitx2-positive cells but not with those expressing Pax7. EOM-derived and LEG-derived EECD34 cells were treated with vehicle, retinoic acid, the RXR agonist bexarotene, the RAR inverse agonist BMS493, or the RXR antagonist UVI 3003. In vitro, fewer EOM-derived EECD34 cells expressed desmin and fused, while more LEG-derived cells expressed desmin and fused when treated with retinoic acid compared to vehicle. Both EOM and LEG-derived EECD34 cells exposed to retinoic acid showed a higher percentage of cells expressing Pitx2 compared to vehicle, supporting the hypothesis that retinoic acid plays a role in maintaining Pitx2 expression. We hypothesize that retinoic acid signaling aids in the maintenance of large numbers of undifferentiated myogenic precursor cells in the EOM, which would be required to maintain EOM normalcy throughout a lifetime of myonuclear turnover. [Display omitted] •Eye and leg muscle express different RAR and RXR levels.•Pitx2+ myogenic precursor cells in extraocular muscles express the RXR receptor.•RA alters rates of Pitx2+ cell proliferation and differentiation.•Increased RA signaling increased numbers of Pitx2+ cells in vitro.•Pitx2+ cells from extraocular and limb muscles respond differently to RA treatment.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2017.10.007