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G Cheng, S Khanna, AP Merriam, P Leahy, FH Andrade, JD Porter; Developmental Gene Expression Profile Underlying Divergence of Extraocular from Other Skeletal Muscles . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1455.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Temporal expression profiling of developing extraocular muscle (EOM) by high-density DNA arrays and electron microscopy. Methods: Affymetrix U34A arrays and routine EM were used to study EOM gene expression/morphogenic patterns at P0 to P45, 3 replicates/age. A self-organizing map cluster analysis identified patterned trends in gene expression. Results: Of 8,800 genes on arrays, 3,385 were expressed in EOM with ≷ 2x changes during the age range. Of these, genes meeting additional significance criteria were grouped into 12 clusters comprising 4 major trends. Type I cluster genes (411) were highly expressed at birth and downregulated by P14; group included cell cycle, transduction and growth regulation factors. Type II cluster genes (104) were absent/low expressers at P0, some upregulated by P7, but most progressively increased starting by P14; group included muscle differentiation genes. Expression of genes in the type III cluster (62) was high at P0, progressively dropped by ∼P14 and then rose thereafter. The trend in the type IV cluster (122) was flat expression across the age range, with ≷ 2x changes embedded in the overall trend. Myosin heavy chain genes directly or inversely mirrored global expression trends: I, EOM-specific, IIA, and IIB myosins were low/absent at birth, but rapidly increased and leveled by P14-21. Likewise, EOM myogenic landmarks tightly correlated with gene expression patterns. P0 EOM lagged other skeletal muscles, with most cells at the myotube stage, small myofibers predominated by P7, and differentiation of the 6 EOM fiber types was evident only after P14. Conclusions: The earliest stages of EOM development resemble those of most other skeletal muscles, but they subsequently differentiate into fiber types unlike any other muscle. Predominant trends in gene expression correlated with ultrastructural differentiation of EOM. Large numbers of genes downregulated from birth, as the secondary wave of myogenesis completed and myofiber differentiation began. Substantive gene regulatory events coincided with or followed eyelid opening at P12 and onset of behaviorally significant eye movements.
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