During C. elegans embryogenesis, myoblasts initially form two rows along the left and right lateral midlines and at ~290 min of development migrate dorsally and ventrally to form the four muscle quadrants present upon hatching (Sulston et al, 1983). As the myoblasts migrate they are still dividing, as are many other cells in their immediate environment. This means the cell-cell contact of cells during migration is dynamic and can vary from animal to animal (Schnabel et al, 1997). This situation creates an environment where the extracellular matrix (ECM) and cell surface contacts are in constant flux, which begs the questions as to how these cells navigate unerringly to their final destination.
In an attempt to identify genes mediating these migrations, I performed an RNAi based screen targeting 776 genes predicted to be members of the extracellular matrix (ECM), or one of its receptors. Using both feeding and injection based RNAi, I was able to identify three genes of interest. Knockdowns of F56B3.2 resulted in paralyzed animals with detached muscle, making it a good candidate for a new component of the muscle attachment complex. F33G12.4 knockdowns resulted in an embryonic arrest phenotype with an abnormal muscle lineage, possibly stemming from polarity defects. The only knockdown that resulted in muscle migration defects was that for lam-2, which encodes for the laminin gamma subunit. Analysis of the lam-2 knockdown, as well as knockdowns for the other laminin subunits, revealed dorsal/ventral migration defects as well as a posterior displacement of the anterior-most ventral muscle cells. Investigation of this posterior displacement has led to the identification of a previously un-described anterior muscle migration event and its dependency upon the extension of muscle processes from the leading cells. / Medicine, Faculty of / Medical Genetics, Department of / Graduate
Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/631 |
Date | 05 1900 |
Creators | Viveiros, Ryan |
Publisher | University of British Columbia |
Source Sets | University of British Columbia |
Language | English |
Detected Language | English |
Type | Text, Thesis/Dissertation |
Format | 8130764 bytes, application/pdf |
Rights | Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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