The Fibroblast Growth Factor Family in the Early Development of Xenopus laevis.

Abstract

The focus of this thesis has been to investigate the requirement for the function of members of the fibroblast growth factor (FGF) family in early Xenopus development both during mesoderm formation in the blastula and later patterning events in the gastrula and neurula. In particular, much attention is focused on the activities and expression of Xenopus embryonic FGF (eFGF) and how this might relate to the perturbations in development which result from the inhibition of the FGF signal transduction pathway following overexpression of a dominant negative FGF receptor (XFD). A detailed description of the XFD phenotype is presented and shows that inhibition of FGF function leads to a reduction in mesoderm formation and a disruption of its normal pattern. Analysis of gene expression in embryos injected with XFD mRNA demonstrates that FGF activity is required for the correct regulation of a subset of genes within the mesoderm at the start of gastrulation. Prominent amongst these is the Xenopus homologue of the Brachyury gene (Xbra). A detailed in situ hybridisation analysis shows that eFGF is coexpressed with Xbra in the mesoderm of the periblastopore region and notochord during neurula and gastrula stages. Later in development they are both expressed in the developing tailbud. FGF-3 is also expressed in the nascent mesoderm and tailbud but also has complex expression domains in the anterior of the embryo. Experiments in this thesis show that not only is FGF function required for the initial expression of mesodermal genes such as Xbra and XmyoD, but is also required to maintain their expression after the period of mesoderm induction. Furthermore, experiments suggest that eFGF and Xbra are components of an autocatalytic regulatory loop that is important for the development of the mesoderm in vertebrates. These data demonstrate a role for FGF activity both during the induction of mesoderm in the blastula and its maintenance and patterning during gastrula and neurula stages.