Date of Award
12-2015
Level of Access Assigned by Author
Campus-Only Thesis
Degree Name
Master of Science (MS)
Department
Zoology
Advisor
Clarissa Henry
Second Committee Member
Mary Tyler
Third Committee Member
Robert Gundersen
Abstract
In the present study, we utilized zebrafish (Danio rerio) embryos and larvae to enhance our understanding of the myomatrix changes during muscle development. Previously, it has been shown that there is a dramatic downregulation of Fibronectin (Fn), during somitogenesis at myotendinous junctions (MTJs). Fn is one key component of Extracellular Matrix (ECM) and plays an essential role for both somite and early muscle development. The replacement of Fn-rich matrix with laminin-rich matrix is essential for normal function of the myotome. Here we investigate the mechanism of Fn degradation during myomatrix remodeling in embryonic stage of zebrafish.
We show that laminin polymerization indirectly promotes Fn degradation at the MTJ, via a matrix metalloproteinase 11(Mmp11)-dependent mechanism. Laminin polymerization is required for both expression and localization of Mmp11 to the MTJ, where Mmp11 is necessary and sufficient for Fn degradation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes Fn-rich MTJ that partially rescues skeletal muscle architecture.
These results identify a mechanism for Fn degradation at the MTJ, highlight crosstalk between different ECM proteins, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn degradation, revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo. These data can be manipulated in many human pathological conditions in which Fn is dysregulated to improve muscle tissue structure and function.
Recommended Citation
Alrowaished, Sarah S., "Laminin Regulates Fibronectin Levels In The Zebrafish Myotendinous Junction Via Matrix Metalloproteinase-11" (2015). Electronic Theses and Dissertations. 2404.
https://digitalcommons.library.umaine.edu/etd/2404