Wellcome Trust PhD Programme for Clinicians at the University of Dundee: 'Regulation and function of Nucleoplasmin3 during neuronal differentiation.' (360G-Wellcome-090808_Z_09_A)

A switch between Fibroblast Growth Factor (FGF) and Retinoic Acid (RA) signalling control onset of neural differentiation in the neural tube with several genes either up or down regulated as the switch occurs. FGF promotes proliferation of neural progenitors and it's down regulation by RA is required for neuronal differentiation. We have recently discovered that Nucleoplasmin3 (NPM3) is down regulated with reduced FGF signalling suggesting it may be co-regulated or is an FGF regulated gene. Nucleoplasmin3 promotes proliferation of mouse Embryonic Stem cells. It's down regulation with FGF signalling raises the possibility that part of the mechanism by which FGF maintains proliferation in the neural tube could be through the function of Nucleoplasmin3. The NPM3 locus is located directly adjacent and upstream to that of Fgf8, a remarkable arrangement that is conserved in different species. NPM3 forms a complex with Nucleoplasmin1 (NPM1) which inhibits NPM1-mediated ribosome biogenesis and this may be involved in cell cycle length and regulation. The role of Nucleoplasmin3 during neural development has not yet been investigated. We aim to understand how signals that direct neural differentiation exert their effects by analyzing the regulation and function of Nucleoplasmin3 during neural development in early chick and mouse embryos.