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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Authors: | Pascal Stuelsatz Andrew ShearerZipora Yablonka-Reuveni |
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Affiliation: | Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA |
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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 Myf5Cre-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 Myf5Cre-driven reporter when compared to the MyoDCre driver. Histological studies of periocular tissue preparations demonstrated the presence of Myf5Cre-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 Myf5Cre-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. |
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Keywords: | Extraocular muscles Satellite cells Fibro/adipogenic progenitors Pericytes and vascular smooth muscle cells Myf5 MyoD Pax3 XLacZ4 Wnt1 Sca-1 |
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