Muscle fiber type plasticity during development and regeneration

Qiaojing Wang, Purdue University

Abstract

The skeletal muscle is a complex tissue mainly composed of a mixture of fast and slow myofibers. The ratio of fast and slow myofibers is built to achieve specific physiological functions and is developed under the control of intrinsic and extrinsic factors. Understanding how myofibers are specified during development and regeneration has several important implications. This project aims to dissect the genetic basis of fast and slow myofiber specification using transgenic mouse models. These mouse models serve as efficient tools for labeling myofibers concurrently expressing fast or slow myosin heavy chain (Myh), or marking myofiber lineages derived from myogenic precursor cells that have once activated fast or slow myosin. Using the lineage labeling mouse model, it was shown that all nascent myofibers unanimously express the slow myosin Myh7 during muscle regeneration. Upon completion of regeneration, however, fast myofibers downregulate Myh7 expression to restore the stereotyped distribution pattern of fast and slow myofibers in the regenerated muscle. In contrast to the ubiquitous expression of Myh7 during regeneration, only a subset of mature fast myofibers had activated the slow Myh7 gene expression during normal development. Moreover, a single mature fast or slow myofiber can be fused from a mixture of precursor cells with different pattern of myosin gene activation. Combining cell lineage tracing and cell culture techniques, the fate of myoblasts that activated the slow muscle specific Myh7 gene was examined. In striking contrast to the dogma that myosin genes are only expressed in terminally differentiated cells, it was shown in this study that myogenic progenitors (myoblasts) activated Myh7 can still proliferate and express Pax7, known to be expressed only in myogenic progenitor but not differentiated cells. Furthermore, the Myh7 activated myoblasts were not limited to become slow muscles, though they had a higher tendency to do so. Together, this study provides compelling evidence that Myh7 can be activated in myogenic progenitors, and that the activation pattern of Myh7 is different during development and regeneration. These results provide novel insight into the regulation of muscle fiber type specification.

Degree

M.S.

Advisors

Kuang, Purdue University.

Subject Area

Animal sciences

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