Fgf9 signalling stimulates Spred and Sprouty expression in embryonic mouse pancreas mesenchyme

Abstract

Epithelial-mesenchymal interactions are critical for normal pancreas development. Fibroblast growth factor (Fgf)-10 is expressed in the pancreatic mesenchyme and its signalling is required for normal growth and regulation of gene expression in the pancreatic epithelium. However, little is known about putative Fgf signalling to the mesenchyme. Here we have examined the embryonic pancreas expression of differentially spliced Fgf receptor isoforms and their targets; the Sprouty (Spry) and Spred family genes which are induced by Fgf signalling. Using qPCR to quantify mRNA levels in microdissected pancreatic epithelium and mesenchyme as well as in FACS isolated Pdx1-GFP(+) and -GFP(-) cell populations we demonstrate that several members of the Spred and Sprouty families are expressed in embryonic mouse pancreas and find Spred1 and -2 as well as Spry2 and -4 to be predominantly expressed in pancreatic mesenchyme. Using embryonic pancreas explant cultures we demonstrate that Spred1/2 and Spry2/4 expression is regulated by Fgf receptor signalling and is increased by treatment with Fgf9, but not by Fgf7 or Fgf10. We extend previous work showing that Fgf9 is expressed in pancreatic mesenchyme, and since Fgf9 is known to activate the mesenchyme-specific "c"-splice forms of Fgf receptors, while Fgf7 and -10 both activate the epithelium-specific "b"-splice forms of Fgf receptors, these results suggest that Fgf signalling is active in the pancreatic mesenchyme, where expression of Spred1/2 and Spry2/4 appear downstream of Fgf9 signalling.