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 Fgf9 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 Fgf9 during pancreatic development, including loss of the transcription factor Barx1. Lastly, we identified conserved expression patterns of FGF9 and receptors in human fetal pancreas, suggesting that FGF9 expressed by pancreatic mesenchyme may similarly affect the development of the human pancreas. [Display omitted] •In early mouse pancreas development Fgf9 is expressed by mesenchyme and mesothelium•Global Fgf9 knockout displays reduced pancreas and stomach size, complete asplenia•Transcriptional programs are perturbed in pancreatic mesenchyme on Fgf9 loss•Expression patterns of FGF9 and receptors are conserved in human fetal pancreas Molecular biology; Cell biology; Developmental biology