Poster abstracts

Poster number 32 submitted by Chung-Ju Yeh

Regulation of satellite cell pool maintenance by FGFR1 and FGFR4

Chung-Ju Yeh (MCDB), Zipora Yablonka-Reuveni (Biologycal Strcuture Department, University of Washington), Christoph Lepper (Department of Physiology and Cell Biology, OSU)

Abstract:
Satellite cells (SCs) are skeletal muscle stem cells that reside under the basal lamina of skeletal muscle fibers. They are responsible for postnatal muscle growth and muscle regeneration. Insufficient numbers of SCs lead to impaired muscle regeneration after acute injury. Therefore, investigating the molecular regulation of SCs is an important issue. The fibroblast growth factor (FGF) signaling pathway plays important roles in skeletal muscle tissue and SCs. The predominantly expressed FGF receptors (FGFRs) in SCs are FGFR1 and FGFR4. However, their role in the regulation of SCs is still unresolved. To investigate the functions of FGFR1 and FGFR4 in SCs, we have generated a mouse model for temporally-controlled genetic inactivation of both FGFR1 and FGFR4 specifically in the SCs. We discovered that upon genetic inactivation of FGFR1 and FGFR4 in the adult, quiescent SC numbers gradually decreased in skeletal muscle tissue over time. This decrease likely results from apoptosis rather than spontaneous activation of quiescent SCs. There was a trend of reduced muscle regeneration, when FGFR1 and FGFR4 were inactivated in SCs. In the activated SCs in single muscle fiber assays, we found that FGFR1/FGFR4-deficient SCs have an increased propensity to differentiate and have decreased proliferation rates. These data indicate that FGFR1 and FGFR4 are required for maintenance of the quiescent SC pool. And in activated SCs, FGFR1 and FGFR4 play a role in balancing proliferation and differentiation.

Keywords: satellite cell, muscle stem cell, FGF