Temporal-spatial patterns of morphogenesis of the musculoskeletal system in the chick thigh and an ultrastructural analysis of the causal mechanisms of muscle separation.

Limb muscles separate from one another in a complex but highly stereotyped sequence and spatial pattern. The process of separation is characterized by the progression of a region of increased extracellular space, the cleavage zone, along the proximodistal axis between the individual muscle anlagen. We analyzed the muscles and cleavage zone during the separation of two representative muscles at the ultrastructural level by electron microscopy to establish an accurate baseline for an analysis of the mechanisms of separation. Comparisons of the morphology and distribution of cells before and after separation reveal characteristic transitions within the cell population of the cleavage zone including a loss of close cell-cell interactions, an increase in extracellular space, the assumption of a more stellate morphology by mesenchyme cells, and a gradual alteration in the composition of the extracellular matrix from one typical of early muscle to one typical of loose connective tissue. Myotubes differentiate between the incipient muscles, ruling out the possibility that the position where muscles will separate is defined by sites where myotubes fail to differentiate. Instead, the myotubes in the cleavage zone gradually diminish in number and appear to be specifically recognized and removed from the cleavage zone by phagocytes. We suggest that the transitions within the cleavage zone are a result of the progressive differentiation of loose connective tissue. If so, then the spatial pattern and process of cleavage is a consequence of spatially programmed cell differentiation. The detailed characterization of the changes that accompany muscle separation at the ultrastructural level provided the basis for describing the formation of all thigh muscles at the light level with great precision. Each muscle has a complex but characteristic pattern of separation along the proximodistal and anteroposterior axes. This complex pattern of separation is not related to the positions of muscles within the thigh, locations of blood vessels, activity patterns of muscles, or innervation patterns. The initial separation patterns are more straightforward than later separations and may be of value in determining the phylogenetic history of limb muscles since the same patterns are common to many tetrapods.PhDBiological SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/105600/1/9023634.pdfDescription of 9023634.pdf : Restricted to UM users only