Molecular mechanisms controlling pancreas versus liver fate decision
Hepatic and pancreatic endoderm share a common set of intrinsic regulatory factors,
such as the FoxA and GATA transcription factors, and are exposed to the same extrinsic
signals, FGF and BMP. However, it remains unclear how the same factors can activate
pancreatic genes, such as Pdx1 and Ptf1a, in the future pancreas, without inducing them
in hepatic progenitors; and analogously, they enable liver development, but not pancreatic
development in the hepatic endoderm. Both intrinsic and extrinsic regulators of this cell fate
decision are under study in our laboratory.
All together, these experiments will define developmental regulators that are able not only
to specify one fate, but also antagonize the other (eg. pancreatic versus hepatic). This knowledge will be
crucial for defining lineage reprogramming strategies of liver to pancreas toward a new cure for diabetes.