Hybrid fibers transform into distinct fiber types in maturing mouse muscles

The role of hybrid fibers as intermediates in fiber type transformations is not completely understood. In some cases hybrids are clearly transitional fibers changing from one type to another, but in others they represent phenotypically stable fibers in normal muscles. In the current study, our goal was to understand the fate of hybrid fibers in fiber type transitions that take place during muscle maturation. Previous studies have reported high proportions of hybrid fibers during postnatal development, but few have followed the fate of these fibers past the time of weaning. We quantified proportions of hybrid fibers in three different mouse skeletal muscles from newly weaned to 6-month-old mice. Hybrid fibers were very prevalent in the brachioradialis (BR) and tibialis anterior (TA) muscles from newly weaned mice, where they constituted 50 and 40% of the fibers, respectively. These hybrids declined steadily to about 15-30% over the next several months. In the soleus muscle the proportion of hybrids did not change, but constituted approximately 20% of fibers. The reduction in IIX/IIB hybrids resulted from different processes in the BR and the TA. In the BR, the reduction was coincident with an increase in type IIX fibers. In the TA, the number of IIX/IIB hybrids was inversely correlated with the proportion of IIB fibers. These patterns reveal that the role of hybrid fibers as intermediates in muscle development is complex. Some hybrid fibers in maturing muscles represent transitional fiber types, while others are phenotypically stable. Moreover, the fate of transitional fibers may be distinct among similar fiber types within different muscles.