Expression and Putative Functions of Fibroblast Growth Factor 10 (Fgf10) in Developing and Adult Skeletal Muscles

Stratford, C (2014) Expression and Putative Functions of Fibroblast Growth Factor 10 (Fgf10) in Developing and Adult Skeletal Muscles. Doctoral thesis, University of East Anglia.

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Abstract

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.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Mia Reeves
Date Deposited: 30 Jun 2015 13:27
Last Modified: 26 Jul 2019 13:34
URI: https://ueaeprints.uea.ac.uk/id/eprint/53422
DOI:

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