The family of fibroblast growth factors (FGFs) are composed of the growth factors involved in a variety of vital phenomena, including development, differentiation, proliferation, and morphogenesis. FGF-1～FGF-10 transmits signals into cells by binding to the FGF receptor (FGFR). Previous publications have suggested the FGF/FGFR signaling pathway is deeply involved in many processes from embryonic development to adult homeostasis.
Activation of FGF/FGFR signaling pathway is also known to be important in organoid cultures. However, proper selection of different FGFR ligands for each organ type is necessary while organoid culture, complicating experimental set up and execution. Therefore, using the universal FGFR ligand “FGF-1”, which shows highly affinity to all the type of FGFR, is expected to be a simple and convenient method for organoid culture. However, FGF-1 is known to be thermally unstable, and at 37°C, which cell-culture is normally being held, the bio-activity is lost within 6 hours, including in the presence of heparin. These factors results in commercially available FGF1 being unable to be used in culture studies.
To solve the problem, MBL provides FGF-Max, a universal FGFR ligand which the thermal stability is highly enhanced by chimerizing FGF-1 and FGF-2.
R-spondin 1 (roof plate-specific spondin 1), also known as Christine 3, is one of the R-spondin family members that regulates to the activation of canonical WNT/β-catenin signaling. In the absence of R-spondin, Frizzled (Fz) is endocytosed by being ubiquitinated by the binding of the ubiquitin ligase RNF43/ZNRF3, Fz on the cell membrane decreases, and Wnt signals are not activated enough. Conversely, in the presence of R-spondin, RNF43/ZNRF3 forms trimers with LGR and R-spondin and is endocytosed, making it unable to ubiquitinate Fz. As a result, Fz on the cell membrane increases, and Wnt signals are strongly activated.1)
Organoid culture is typically utilized niche factors that act on Wnt, EGF, BMP and Notch signals that control stem cell differentiation. Among these signals, R-spondin 1 contributes to the activation of Wnt signals.
Recombinant Human R-spondin 1 (Code No. J2-004) is a protein derived from the gene encoding human R-spondin 1 (region; 21-146 aa) expressed in E. coli. This region contains a bioactive fragment comprising the two cysteine-rich furin-like domains (Fu1 and Fu2). Fu1 binds to the extracellular domain of ZNRF3*1 and RNF43*2, and Fu2 binds to the extracellular domain of LGR4/5/6*3. 2)
*1 zinc and ring finger 3, *2 ring finger protein 43, *3 leucine-rich repeat-containing G-protein coupled receptors 4/5/6