Analysing the role of FGF signalling in pluripotency and skeletal muscle development.

During development, totipotent stem cells give rise to a host of
specialised, differentiated cell types. This process involves the
progressive restriction of developmental potential, and requires the highly
coordinated activation of sets of regulatory genes in specific groups of
cells in the developing embryo in response to cell signalling. The
fibroblast growth factor (FGF) signalling pathway is an important
regulator of gene expression during development. Our previous work
indicates that FGF signalling activates and maintains the expression of
key developmental regulators, such as the transcription factor MyoD; a
myogenic regulatory factor that can orchestrate the process of
differentiation of skeletal muscle cells from stem cells. During vertebrate
development skeletal muscle cells arise from a pool of stem cells in the
posterior of the developing embryo. Recent evidence indicates that
properties of stem cells are regulated by a number of pluripotency
factors, including Oct4, c-Myc, Lin28, and Nanog. This project will
investigate the interplay of FGF signalling, MyoD and pluripotency factors
in muscle development in vivo using non-mammalian vertebrate animal
models (Xenopus and zebrafish).
This project will take make use of the advantages of frog and fish
embryos for investigating cell lineage, cell signalling and gene expression

during development. We will make use CRISPR/Cas9 mediated gene
editing in frogs and fish to investigate the role of the FGF signalling and
the pluripotency factors c-Myc, Lin28, and Vent2 (nanog) in skeletal
muscle development. Manipulating the FGF signalling using
pharmacological inhibition to inactivate and inducible FGF receptors to
overstimulate the pathway will be the initial approach to uncovering the
regulation of muscle determination, maintenance and differentiation
during development. The student will also undertake some
embryological manipulations of frogs embryos to determine the
pluripotent nature of the cells in the posterior mesoderm.