All mature pancreatic cell types arise from a pool of organ-specific multipotent progenitor cells. Cell-intrinsic and cell-extrinsic cues promote the proliferation and cell fate commitment of these progenitor cells but what integrates these cues during pancreatic morphogenesis? Maike Sander and co-workers now report that the transcription factor Sox9 forms the centrepiece of a gene regulatory network that controls pancreatic development (see ). Pancreatic progenitor-specific ablation of Sox9 during early mouse pancreatic development, they report, leads to cell-autonomous loss of fibroblast growth factor receptor 2b (Fgfr2b), which is required to transduce mesenchymal Fgf10 signals. In turn, Fgf10 is required to maintain progenitor expression of Sox9 and Fgfr2b. Perturbation of this Sox9/Fgfr2b/Fgf10 feed-forward expression loop results in pancreas-to-liver fate conversion. Given that Fgf signalling is necessary for pancreatic progenitor cell proliferation, the researchers propose that a Sox9/Fgf feed-forward loop coordinately controls organ fate commitment and progenitor cell expansion in the developing pancreas, a finding that may advance efforts to generate insulin-producing cells for therapeutic use.
