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J. V. Gerhart, J. Elder, J. Pfautz, K. DuPrey, C. Neely, A. Menko, K. Knudsen, M. George-Weinstein; Epiblast-Derived Skeletal Muscle Stem Cells Promote Eye Development. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3213.
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The epiblast layer of the early embryo contains a subpopulation of skeletal muscle stem cells (e-skm stem cells) that express MyoD mRNA, the G8 antigen and Noggin, an inhibitor of bone morphogenetic proteins (BMPs). Ablation of e-skm stem cells in the epiblast results in protrusion of organs through the ventral body wall and eye malformations. The goals of this study were to: (1) determine the sites of incorporation of e-skm stem cells in the developing eye, (2) examine e-skm stem cells for expression of Noggin within ocular tissues, and (3) characterize the eye defects that arise when e-skm stem cells are ablated in the epiblast.
E-skm stem cells were fluorescently labeled in the stage 2 chick embryo with a monoclonal antibody that binds to the G8 antigen. The distribution of e-skm stem cells in the developing eye was determined by epifluorescence microscopy. Expression of Noggin in e-skm stem cells was analyzed by in situ hybridization. E-skm stem cells were ablated in the epiblast by lysing G8 labeled cells with complement. Ablated embryos were supplemented with exogenous Noggin by implanting beads soaked in human recombinant Noggin. The eyes were examined in whole embryos and tissue sections.
E-skm stem cells were tracked into the anterior/lateral neural plate and adjacent ectoderm that form the optic cup and lens placode, respectively. In older embryos, Noggin expressing e-skm stem cells were found in the optic cup, lens and periocular mesenchyme. Ablation of e-skm stem cells in the epiblast produced eye defects of varying severity, including clinical anopthalmia, micropthalmia, aniridea, malformed lenses and optic cups, and retinal looping. Supplementation of ablated embryos with exogenous Noggin reduced the severity of eye defects.
E-skm stem cells are required for normal eye development. Release of Noggin by e-skm stem cells may regulate BMP signaling in the lens, optic cup and periocular mesenchyme.
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