The adult mammalian spinal cord contains a multitude of neurons that are critical for motor and sensory functions (1). As with most other regions of the central nervous system (CNS), spinal neurons are generated mostly during embryonic development, under the influence of local and distant regulatory factors. Fibroblast growth factors (FGFs) and signalling through their receptors (FGFRs) play critical roles in the formation of diverse organs - from limbs to the brain, by regulating cell identity and rates of cell proliferation, differentiation and migration (2). Based on existing expression pattern studies, we hypothesise that FGF signalling regulates the specification and identity of distinct neurons during embryogenesis. We will test this hypothesis by examining the spinal cord of mouse embryos derived from transgenic mice that allow deletion or over-expression of FGFs, or their receptors, in specific populations of spinal neurons. In vivo analysis will be complemented by in vitro studies, comparing the behaviour and fate of wild type and FGF-deficient or FGF-overexpressing spinal cord cells grown in culture. These studies will provide novel insights into the functioning of FGF signalling during spinal cord development and should inform studies aimed at treating diseases that afflict this tissue, such as Motoneuron disease.

This project will train the candidate in a valuable array of cellular and molecular techniques, including isolation and handling of DNA, RNA and protein, gene cloning, neural cell culture, Immunolabelling, high-resolution microscopy and bioinformatics. Furthermore, the candidate will become fully familiar with mouse genetics and transgenesis as tool for dissecting gene function in vivo. The candidate will also have the opportunity to undertake a host of professional development training modules, offered by UEA's graduate school, to enhance his/her professional skills.

(i)     Levine et al (2012) Spatial organization of cortical and spinal neurons controlling motor behavior. Curr Opin Neurobiol. 22: 812-21

(ii)     Itoh and Ornitz (2011) Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease. J Biochem. 149: 121-30.