Loss of Fgf9 in Mice Leads to Pancreatic Hypoplasia and Asplenia

Pancreatic development requires spatially and temporally controlled expression of growth factors derived from mesenchyme. Here, we report that in mice the secreted factor Fgf9 is expressed principally by mesenchyme and then mesothelium during early development, then subsequently by both mesothelium and rare epithelial cells by E12.5 and onwards. Global knockout of the gene resulted in the reduction of pancreas and stomach size, as well as complete asplenia. The number of early Pdx1+ pancreatic progenitors was reduced at E10.5, as was proliferation of mesenchyme at E11.5. Although loss of Fgf9 did not interfere with differentiation of later epithelial lineages, single-cell RNA-Sequencing identified transcriptional programs perturbed upon loss of during pancreatic development, including loss of the transcription factor . Lastly, we identified conserved expression patterns of and receptors in human fetal pancreas, suggesting that expressed by pancreatic mesenchyme may similarly affect the development of the human pancreas.