Expression and Putative Functions ofFibroblast Growth Factor 10 (Fgf10) inDeveloping and Adult Skeletal Muscles

Although the genetic regulation of vertebrate myogenesis during early development has been well studied, the intrinsic mechanisms controlling muscle fiber-type specification and maturation are much less understood. Fibroblast growth factors (Fgfs) are potent regulators of myoblast proliferation and differentiation in vitro. However, their in vivo functions in myogenesis have yet to be fully elucidated. This study was prompted by the discovery of Fgf10 expression in adult mouse skeletal muscles. Using an Fgf10-nLacZ reporter line, I set out to characterize this novel expression pattern in order to learn more about Fgf10’s putative function/s. I have shown that intriguingly Fgf10 is only expressed in a subset of adult muscles, which are predominantly fasttwitch. The expression begins during late embryonic development, but is subsequently conserved and restricted to the same muscles throughout adult life. Moreover, within each positive muscle, only a subset of myofibers expresses Fgf10. Immunolabeling with Pax7 antibodies showed that a subpopulation of Fgf10-expressing myonuclei expresses this satellite stem cell marker. To delineate the function of Fgf10, I examined the limbs of newborn Pax3- Cre::Fgf10(flox/-) double transgenic mice, and I discovered that myofiber growth was impaired in Fgf10-expressing muscles. Moreover, the distal myofiber organization was severely disorganized in certain muscles, indicating defective attachment to the bone. This suggested that Fgf10 might also be regulating tendon development. Collectively, these studies suggest that Fgf10 plays diverse roles in the developing musculoskeletal system, including the formation and maturation of fast fibers, and also in tendon development. Fgf10 may also play a role in muscle regeneration in response to injury, however this 3 remains to be tested in physiological challenge and regeneration paradigms in vivo.