Author

Robert Jones

Date of Award

5-2007

Level of Access

Campus-Only Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry

Advisor

Clarissa A. Henry

Second Committee Member

Mary S. Tyler

Third Committee Member

Gregory D. Mayer

Abstract

Normal skeletal muscle development involves the specification and morphogenesis of muscle fibers that attach to tendons. The resulting junction of muscle and tendon, the myotendonous junction (MTJ), then functions as an integrated unit to transmit force to the skeletal system and to stabilize joints. In teleost fishes, the basement membrane between developing myotomes, that ultimately becomes the myotome boundary, is analogous to the mammalian tendon and serves as the primary source of force transmission. Embryos deficient for the basement membrane protein laminin exhibit phenotypically shorter, and sometimes round, fast twitch muscle cells, disrupted slow fiber migration and they often lack the ability to maintain myotome boundary (tendon) integrity. In both mutants for laminin (31 and yl, and their morpholino oligonucleotide (MO) injected counterparts, we clearly see these shorter muscle cells which demonstrates the importance of laminin's role in cell-matrix adhesion during myotome morphogenesis. Over time, the majority of these short fast fibers exhibit the ability to recover by some yet unknown mechanism, but they are often misoriented or able to invade neighboring myotomes. When laminin mutants are incubated in cyclopamine, to inhibit the hedgehog signaling pathway necessary for slow muscle specification, fast fibers fail to recover at all and the myotome boundaries are intact. Using genetic mosaic analysis we are able to show that the amount of laminin secreted by transplanted wild-type cells in a mutant embryo is insufficient to rescue fast fiber elongation, though the transplanted cells themselves are capable of elongating.

Files over 10MB may be slow to open. For best results, right-click and select "save as..."

Share