Sarcomerogenesis

Abstract: The direct determination, by counting, of the number of sarcomeres in series along the length of single teased muscle fibres taken from mice of different ages showed that the increase in fibre length during normal growth is accompanied by a large increase in sarcomere number. The greatest increase occurs during the 3 weeks after birth. By counting the number of muscle fibre nuclei in single teased fibres it was shown that the number of nuclei per fibre increases with age, and that this increase continues beyond the point at which the fibres have ceased to grow in length. It is suggested that post-natal increase in nuclear number is associated with both increase in length and increase in girth of the muscle fibres. By injecting tritiated adenosine into young mice, an attempt was made to label newly formed actin filaments and ribosomes and thus to determine the region where new sarcomeres are laid down during increase in fibre length. Using autoradiography and scintillation counting it was shown that the radioactive label was incorporated more into the ends than into the middle regions of the muscles. The implication of these findings is that new sarcomeres are added on serially at the ends of the muscle fibres. An investigation, at the ultrastructural level, of muscle fibres taken from foetal and newborn mice indicates that the end of the fibre is a region of active development. This area is characterized by numerous ribosome formations and by myofilaments which are not organized into myofibrils. Cells which can occasionally be seen fusing with the end regions of young muscle fibres indicate a possible way in which nuclei are added to the growing fibre. Immobilization experiments have shown that it is possible to alter both the rate and the extent of the post-natal increase in sarcomere number. Immobilization of limb joints, by means of plaster casts, so that the muscle is held in either the extended or the shortened position results in the number of sarcomeres along the fibres falling far short of that in the fibres from control muscles. Removal of the restriction is followed by a rapid increase in the number of sarcomeres in series and a return to the normal level within a period of about 4 weeks. These experiments indicate that for normal growth to occur, it is important for a muscle to be able to contract isotonically.

Abstract: Myofibrillogenesis in striated muscles is a highly complex process that depends on the coordinated assembly and integration of a large number of contractile, cytoskeletal, and signaling proteins in...

Abstract: Cardiac organogenesis and pathogenesis are both characterized by changes in myocyte shape, cytoskeletal architecture, and the extracellular matrix (ECM). However, the mechanisms by which the ECM influences myocyte shape and myofibrillar patterning are unknown. We hypothesized that geometric cues in the ECM align sarcomeres by directing the actin network orientation. To test our hypothesis, we cultured neonatal rat ventricular myocytes on islands of micro-patterned ECM to measure how they remodeled their cytoskeleton in response to extracellular cues. Myocytes spread and assumed the shape of circular and rectangular islands and reorganized their cytoskeletons and myofibrillar arrays with respect to the ECM boundary conditions. Circular myocytes did not assemble predictable actin networks nor organized sarcomere arrays. In contrast, myocytes cultured on rectangular ECM patterns with aspect ratios ranging from 1:1 to 7:1 aligned their sarcomeres in predictable and repeatable patterns based on highly localized focal adhesion complexes. Examination of averaged alpha-actinin images revealed invariant sarcomeric registration irrespective of myocyte aspect ratio. Since the sarcomere sub-units possess a fixed length, this observation indicates that cytoskeleton configuration is length-limited by the extracellular boundary conditions. These results indicate that modification of the extracellular microenvironment induces dynamic reconfiguring of the myocyte shape and intracellular architecture. Furthermore, geometric boundaries such as corners induce localized myofibrillar anisotropy that becomes global as the myocyte aspect ratio increases.