Regulation of FGF signaling: Recent insights from studying positive and negative modulators

Fibroblast growth factor (FGF) signaling is involved in a multitude of biological processes, while impairment of FGF signaling is implicated in a variety of human diseases including developmental disorders and cancer. Therefore, it is not surprising that FGF activity is regulated at multiple and distinct levels. This review focuses on positive and negative modulation of the FGF signal exemplified by recently identified protein modulators anosmin-1, fibronectin-leucine-rich transmembrane protein 3 (FLRT3) and similar expression to FGF (Sef). We examine how these proteins regulate FGF signaling at multiple levels and across species. Finally, we describe the role of these regulators in human disease.