Extending the family table: Insights from beyond vertebrates into the regulation of embryonic development by FGFs

Abstract

Since the discovery of Fibroblast Growth Factors much focus has been placed on elucidating the roles for each vertebrate FGF ligand, receptor, and regulating molecules in the context of vertebrate development, human disorders and cancer. Studies in human, mouse, Xenopus, chick, and zebrafish have gone a long way to help us understand [AS1]which FGFs are involved in which processes. However, in recent years, as more genomes are sequenced, more information is becoming available from many non-vertebrate models and a more complete picture of the FGF superfamily as a whole is emerging. In some cases less redundancy in the FGF signaling system in invertebrate models may allow for more mechanistic insights. Studies in cnidaria have highlighted how ancient FGF signaling is, and helped provide insight into the evolution of the FGF gene family. Work in C. elegans has shown that different splice forms can be used for functional specificity in invertebrate FGF signaling. Comparing FGFs from Ciona to those in vertebrates and FGFs from Tribolium to Drosophila reveals some important clues as to the process of gene loss, duplication and subfunctionalization of FGFs throughout evolution. Finally, comparing all members of the FGF ligand superfamily reveals variability in many properties, which may point to a feature of FGFs as being highly adaptable with regards to protein structure and mechanism. Further studies on FGF signaling outside of vertebrates is likely to complement work in vertebrates by contributing many insights to the FGF field as a whole and providing unexpected information that could be used for medical applications.

FGF signaling supports Drosophila fertility by regulating development of ovarian muscle tissues

“…Keeping FGF signaling properly regulated is important for normal ovary development, but its exact role in supporting gonad development is unclear. Furthermore, FGF signaling is conserved as its biological roles and structural properties appear similar in Drosophila and higher vertebrates (Huang and Stern, 2005; Tulin and Stathopoulos, 2010b). Studies of how FGF signaling impacts Drosophila ovary morphogenesis have the potential to provide novel insights into conserved functions and/or regulatory mechanisms acting in other organisms, including vertebrates.…”

Synchronous and symmetric migration of Drosophila caudal visceral mesoderm cells requires dual input by two FGF ligands

“…Although studies in vertebrate systems postulate that heterodimeric FGF ligand combinations do activate FGFRs and structural studies of FGF-FGFR interactions support this view (Plotnikov et al, 2000;Zhang et al, 2006), to our knowledge, no definitive experimental evidence exists. Over 120 FGF-FGFR interactions are presumed to function in vertebrates (Zhang et al, 2006), whereas evidence for activity of three combinations has been presented in Drosophila (Kadam et al, 2009;Tulin and Stathopoulos, 2010). Here, taking advantage of this simplified receptor-ligand system in Drosophila, we studied the differential effects of multiple FGF ligands in activating the same FGFR receptor and how this contributes to symmetric and synchronous migration of CVM cells.…”

Genetic insights into the mechanisms of Fgf signaling

“…A fifth Fgfr-like protein (FgfrL1) has also been identified that lacks an intracellular tyrosine kinase domain and likely negatively regulates Fgfrs by sequestering ligand (for review, see Trueb et al 2013). Fgf signaling is required throughout metazoans and is commonly studied in organisms ranging from cnidarians to humans (Tulin and Stathopoulos 2010). These studies indicate that Fgf signaling is required pleiotropically during development and also regulates multiple homeostatic and reparative functions in adults (Ornitz and Itoh 2015).…”