Fibroblast Growth Factor Signaling and the Function and Assembly of Basement Membranes

Abstract

Publisher Summary This chapter focuses on the contribution of the extracellular matrix (ECM) to signal transduction during early development and epithelial differentiation. Special emphasis is given to basement membranes (BMs) and fibroblast growth factors (FGFs) as studied in embryoid body (EB) cultures. The chapter focuses on the interactions between the BM separating the extra embryonic endoderm and the epiblast of the mammalian embryo. These early stages of development bridge the differentiation of the preimplantation blastocyst into the pregastrulation egg-cylinder embryo. Gene targeting revealed the delicate specificity of laminin isotypes. The role of fibroblast growth factor signaling in early embryogenesis is suggested by the requirement of fibroblast growth factor-4 (Fgf4) for trophectoderm and endoderm development and by the finding that dominant negative fibroblast growth factor receptor (FGFR) mutation elicited by expressing truncated Fgfr2 cDNA in embryonic stem (ES) cells abolishes endoderm and ectoderm differentiation in the EB, where multiple Fgfr are expressed in synchrony. The mutant defects largely follow the specific gene expression patterns of the laminin isotypes. FGFs are distinguished by their affinity to heparin and once were denominated as heparin-binding growth factors. Localized expression and localized function of individual members of a gene family reflect localized transcriptional regulation—that is, the availability of specific transcription factors at specific locations. Local regulation may or may not be associated with locally specific function.