The determinants of muscle fiber type during embryonic development

SYNOPSIS. Most vertebrate skeletal muscles consist of a heterogeneous array of muscle fiber types that are distinguishable, in part, by differences in their contractile protein isoform content. It is often suggested that the information necessary for directing the development of these fiber types is derived from interactions with factors outside the muscle fibers themselves and, in particular, with innervating motoneurons. However, recent data from this and other laboratories indicate that the emergence of fiber specialization within developing muscle is not dependent on innervation at all. These studies recognize two periods of embryonic fiber specialization. The first occurs during early embryonic development as individual muscles are formed from primary generation fibers expressing different myosin isoform types. The formation of these "early" muscle fiber types and their characteristic distributions within and among different muscles are not dependent on interactions with innervating motoneurons. Furthermore, myoblasts isolated from "early" embryonic muscle tissue and cultured in vitro display the same heterogeneity of myosin expression as the primary generation fiber types in ovo, suggesting that the differences in expression among early muscle fiber types are preprogrammed within their myoblasts. The second period occurs "late" in development after the major morphological events of limb formation are complete and the initial pattern of fiber types has been established. It is during this period that massive growth of most muscles occurs which is due, in part, to the formation of a secondary generation of muscle fibers. These secondary generation fibers in ovo and the cultured myotubes derived from "late" embryonic myoblasts exhibit a single myosin phenotype (e.g., fast). The transition from "early" to "late" embryonic phases is accompanied by a change in fast myosin heavy chain expression and is blocked by agents that disrupt neuromuscular contacts.