Mechanisms regulating skeletal myoblast development
Abstract
Analysis of whether Fibroblast Growth Factors (FGFs) are important regulators of myoblast development has been performed. My results show that FGFs and their receptors are central during embryonic muscle development as well as hypertrophy in adult muscle in vivo. Using a defined hypertrophy model in adult chicken, a role for FGFs was assayed. In hypertrophic muscle groups, specific FGFs were increased and decreased, indicating a precise role for individual FGFs in adult muscle hypertrophy. FGF receptors were found to play a role in regulating fusion of myoblasts. Using the wild-type BC3H1 and fusion competent BC3H1#1 cells, a correlation was established between fusion ability and the FGF-Receptor expression pattern. In wild-type 13C3H1 but not BC3H1#1 cells, Fibroblast Growth Factor-Receptor 2 (FGFR-2) is expressed. This correlation was confirmed by expression of FGFR-2 in the fusion competent C2C12 myoblast cell line. Transfection of FGFR-2 in myoblasts reduced fusion, and increased the number of unfused, differentiated myocytes. In addition, transfections showed that both FGFR-2 and Fibroblast Growth Factor-Receptor 1 (FGFR-1) regulate the ratio differentiated and undifferentiated cells. These results suggest that exact expression pattern of FGF-Receptors may be important in myoblast development. Furthermore, my results indicate that the ability of the myoblasts to undergo fusion is closely linked to the de-differentiation capabilities of myocytes. The differentiation state of myocytes appears determining for the response to mitogen stimulus. Using the fusion competent BC3H1#1 subclone, it is demonstrated that once myoblasts fuse, they lose the ability to de-differentiate, and instead react to mitogens with a hypertrophic response. These results expand on studies previously published and add to the roles of FGFs in myoblast development.
Degree
Ph.D.
Advisors
Hannon, Purdue University.
Subject Area
Cellular biology|Molecular biology
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