Determination of downstream targets of FGF signalling using gene trap and cDNA subtractive approaches

Signalling through the fibroblast growth factor family (FGF) of ligands is essential for normal mammalian embryonic development. At a cellular level, many details of the molecular basis of the signal transduction process have been uncovered, but our knowledge of the identity of the downstream effectors of the FGF signal in the developing embryo remains limited. We have used two independent approaches to begin to identify downstream targets of FGF signalling in the embryo: (1) a gene trap approach and (2) cDNA subtraction, using mouse embryonic stem (ES) cells as a cellular system representative of an early window on the developing embryo. Both approaches led to the identification of a number of targets of FGF signalling, and we provide data to show that the chaperone Mrj, the tumour antigen Tum, collapsin mediator response protein Crmp, a novel transcriptional repressor Nac1 and ribophorin are all differentially regulated following FGF signalling. Independent gene trapping of Mrj previously indicated a role for the gene in embryogenesis [Development 126 (1999) 1247], and we present transcript data implicating a number of the newly isolated FGF target genes in different embryonic processes. [Copyright &y& Elsevier]