SPATIAL AND TEMPORAL PATTERNS OF MYOSIN HEAVY-CHAIN EXPRESSION IN DEVELOPING RAT EXTRAOCULAR-MUSCLE

The present study describes transitions in myosin heavy chain expressi on in the extraocular muscles of rats between the ages of E17 and adul t. The unique phenotype of the extraocular muscle is reflected in its fibre type composition, which is comprised by six distinct profiles, e ach defined by location (orbital versus global layer) and innervation pattern (single versus multiple terminals). During extraocular muscle myogenesis, developmental myosin heavy chains were expressed in both p rimary and secondary fibres from embryonic day E17 through the first p ostnatal week. At this time, the downregulation of developmental myosi n heavy chain isoforms began in the global layer in a fibre type-speci fic manner, reaching completion only after the first postnatal month. By contrast developmental isoforms were retained in the overwhelming m ajority of orbital layer fibres into adulthood and expressed different ially along the length of these fibres. Fast myosin heavy chain was de tected pre- and postnatally in developing secondary fibres and in all of the singly innervated fibre types and one of the multiply innervate d fibre types in the adult. As many as four fast isoforms were detecte d in maturing extraocular muscle, including the extraocular muscle-spe cific myosin heavy chain. Slow myosin heavy chain was expressed in pri mary fibres throughout development and in one of the multiply innervat ed fibre types in the adult. In contrast, the pure fast-twitch retract or bulbi initially expressed slow myosin heavy chain in fibres destine d to switch to the fast myosin heavy chain developmental programme. Ba sed upon spatial and temporal patterns of myosin heavy chain isoform t ransitions, we suggest that epigenetic influences, rather than purely myogenic stage-specific factors, are critical in determining the uniqu e extraocular muscle phenotype.