Signals from the endothelium play a pivotal role in pancreatic lineage commitment. As such, the fate of the epithelial cells relies heavily on the spatiotemporal recruitment of the endothelial cells to the embryonic pancreas. While it is known that Vegf-A secreted by the epithelium recruits the endothelial cells to the specific domains within the developing pancreas, the mechanism that controls the timing for such recruitment is poorly understood. Here, we assessed the role of focal adhesion kinase (FAK) in mouse pancreatic development based on our observation that the presence of the enzymatically active form of FAK (pFAK) in the epithelial cells is inversely correlated with vessel recruitment.
To study the role of FAK in the pancreas, we conditionally deleted the gene encoding focal adhesion kinase in the developing mouse pancreas. We found that homozygous deletion of the Fak gene during embryogenesis resulted in ectopic epithelial expression of Vefg-A, abnormal endothelial recruitment and a delay in endocrine and acinar cell differentiation. The heterozygous mutants were born with no pancreatic phenotype but displayed gradual acinar atrophy due to cell polarity defects in exocrine cells.
Together, our findings imply a role for FAK in controlling the timing of pancreatic lineage commitment/differentiation in the embryonic pancreas by preventing endothelial recruitment to the embryonic pancreatic epithelium.
