Poster abstracts

Poster number 24 submitted by Chung-Ju Yeh

Regulation of satellite cell pool maintenance by FGFR1 and FGFR4

Chung-Ju Yeh (Molecular, Cellular, and Developmental Biology Program, The Ohio State University), 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. 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. Western blot experiments revealed that FGFR1/FGFR4 may regulate activated SCs through the ERK signaling pathway. However, no significant change in muscle regeneration was observed when FGFR1 and FGFR4 were inactivated in SCs. These data indicate that FGFR1 and FGFR4 are required for the SC pool maintenance in quiescent SCs and play a role in balancing proliferation and differentiation in activated SCs.

Keywords: satellite cell, muscle stem cell, FGF