The exocrine pancreas produces and transports secretions necessary for intestinal food absorption. Defects in exocrine pancreas development or function can lead to malabsorption and malnutrition, and in more severe cases can predispose to pancreatitis or pancreatic cancer. Our lab identified a novel regulator of exocrine pancreas development and homeostasis, the homeobox gene Prox1. We found that Prox1 deficiency impairs branch formation (arrows in A) and acinar differentiation in the developing pancreas, and causes extensive loss of acinar tissue (arrows in B) and lipomatosis (arrowhead in B) in the postnatal mouse pancreas. We also found that ductal cells (arrowheads in C) but not acinar cells (arrows in C) express Prox1 in the postnatal pancreas, and determined that ectopic Prox1 expression disrupts cell polarity (arrows in D [asterisk shows a normal acinus]) and secretory pathway expression in mature acinar cells. We will use our in vivo mouse models in combination with ex vivo embryonic pancreas cultures, imaging techniques and in silico approaches, to determine how Prox1 coordinates epithelial morphogenesis and acinar differentiation in the embryonic pancreas, and to unravel how cell polarity is established in acinar cells.
Prox1-deficiency impairs branching morphogenesis and acinar development
A.) Defective branching morphogenesis
B.) Acinar cell loss
Ectopic Prox1-expression impairs acinar maturation
C.) Mature acinar cells do not express Prox1
D.) Ectopic Prox1 expression disrupts acinar cell polarity