Investigation into the FGF-mediated regulation and function of rasl11b during early Xenopus development

Fibroblast growth factor (FGF) signalling is essential for the initiation and regulation of multiple developmental processes including gastrulation, mesoderm induction and anteroposterior patterning. Despite an extensive understanding of FGF signal transduction via receptor tyrosine kinases (RTKs), the exact mechanism of FGF target gene expression has yet to be fully elucidated. Capicua (CIC) is a labile transcriptional repressor of RTK target genes, with evidence suggesting that CIC may act in the FGF signalling pathway. Therefore, we hypothesise that the expression of a subset of FGF target genes is reliant upon the ERK-mediated relief of CIC transcriptional repression. In this study, gene-level RNA-Seq analysis of CIC knockdown and FGF overexpressing Xenopus tropicalis embryos was undertaken, which identified a statistically significant overlap of genes upregulated in both sets of embryos. One of the genes significantly upregulated following CIC knockdown and FGF overexpression was rasl11b which encodes a Ras-like small GTPase with a currently uncharacterised role in development. This study has defined the domains of rasl11b expression during X. tropicalis development, particularly within the pre-somitic mesoderm (PSM). Manipulation of FGF signalling shows that during gastrulation rasl11b expression in the early mesoderm is FGF-dependent, but later in development, rasl11b expression in the PSM is regulated independently of FGF signalling. Furthermore, this study suggests that Rasl11b may upregulate FGF activity in the PSM during somitogenesis. Dysregulation of FGF signalling and/or CIC transcriptional repression is associated with a range of disorders and cancers. Consequently, understanding the molecular mechanisms of FGF target gene expression and function will contribute to the development of more effective therapeutics for developmental disorders and cancer.