The Role of Prox1 during Mouse Pancreas Organogenesis

The pancreas is a mixed (exocrine and endocrine) glandular organ that is important for food digestion and glucose homeostasis. Developmental anomalies or disorders that affect normal pancreas homeostasis may cause various life-threatening diseases such as pancreatitis, diabetes, cystic fibrosis, and pancreatic cancer. In the past two decades, an increasing number of studies have begun to unravel the molecular and cellular mechanisms regulating mammalian pancreas organogenesis. The information extracted from these studies should be valuable both, to better understand the etiology of some pancreatic diseases, and to design new therapeutic tools to cure those diseases. A recent study reported expression of the homeodomain transcription factor Prox1 in the presumptive pancreatic region of mouse embryos1. This finding raised the possibility that, similar to other tissues, proper pancreas development requires the function of Prox1. The studies of my Ph.D thesis sought to uncover the role of Prox1 during mouse pancreas organogenesis. First, the expression of Prox1 in the developing pancreas was thoroughly characterized and the pancreatic tissues of Prox1-nullizygous embryos were analyzed (Chapter 2). Second, since Prox1-nullizygous embryos die at around embryonic day (E) 14.5, we generated a (Prox1loxP/loxP novel mouse model ;Pdx1.Cre) with conditional inactivation of Prox1 in pancreatic progenitors, to investigate whether loss of Prox1 function affects late aspects of pancreas organogenesis (Chapter 3). Third, upon identifying Opn as a novel pancreatic gene, we performed an extensive analysis of its expression in the pancreas of mouse embryos and adults and characterized this organ of Opn-nullizygous mice (Chapter 4).