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Dev Biol. 2014 Jan 15;385(2):366-79. doi: 10.1016/j.ydbio.2013.08.010. Epub 2013 Aug 19.

Ancestral Myf5 gene activity in periocular connective tissue identifies a subset of fibro/adipogenic progenitors but does not connote a myogenic origin.

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Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA.
Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address:


Extraocular muscles (EOM) represent a unique muscle group that controls eye movements and originates from head mesoderm, while the more typically studied body and limb muscles are somite-derived. Aiming to investigate myogenic progenitors (satellite cells) in EOM versus limb and diaphragm of adult mice, we have been using flow cytometry in combination with myogenic-specific Cre-loxP lineage marking for cell isolation. While analyzing cells from the EOM of mice that harbor Myf5(Cre)-driven GFP expression, we identified in addition to the expected GFP(+) myogenic cells (presumably satellite cells), a second dominant GFP(+) population distinguished as being Sca1(+), non-myogenic, and exhibiting a fibro/adipogenic potential. This unexpected population was not only unique to EOM compared to the other muscles but also specific to the Myf5(Cre)-driven reporter when compared to the MyoD(Cre) driver. Histological studies of periocular tissue preparations demonstrated the presence of Myf5(Cre)-driven GFP(+) cells in connective tissue locations adjacent to the muscle masses, including cells in the vasculature wall. These vasculature-associated GFP(+) cells were further identified as mural cells based on the presence of the specific XLacZ4 transgene. Unlike the EOM satellite cells that originate from a Pax3-negative lineage, these non-myogenic Myf5(Cre)-driven GFP(+) cells appear to be related to cells of a Pax3-expressing origin, presumably derived from the neural crest. In all, our lineage tracing based on multiple reporter lines has demonstrated that regardless of common ancestral expression of Myf5, there is a clear distinction between periocular myogenic and non-myogenic cell lineages according to their mutually exclusive antecedence of MyoD and Pax3 gene activity.


Extraocular muscles; Fibro/adipogenic progenitors; Myf5; MyoD; Pax3; Pericytes and vascular smooth muscle cells; Satellite cells; Sca-1; Wnt1; XLacZ4

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