title: Ancestral Myf5 gene activity in periocular connective tissue identifies a subset of fibro/adipogenic progenitors but does not connote a myogenic origin.
abstract: 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.
authors: Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Pascal
authors: P
authors: Stuelsatz
authors: Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Andrew
authors: A
authors: Shearer
authors: Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: reuveni@uw.edu.
authors: Zipora
authors: Z
authors: Yablonka-Reuveni
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D005123:Eye; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*
chemical_list: C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D049452:Green Fluorescent Proteins
keywords: Extraocular muscles; Fibro/adipogenic progenitors; Myf5; MyoD; Pax3; Pericytes and vascular smooth muscle cells; Satellite cells; Sca-1; Wnt1; XLacZ4
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