Key events of pancreas formation are triggered in gut endoderm by ectopic expression of pancreatic regulatory genes

The mechanisms by which the epithelium of the digestive tract and its assoc iated glands are specified are largely unknown. One clue is that several tr anscription factors are expressed in specific regions of the endoderm prior to and during organogenesis. Pdx-1, far example, is expressed in the duode num and pancreas and Pdx-1 inactivation results in an arrest of pancreatic development after buds formation. Similarly, ngn3 is transiently expressed in the developing pancreas and a knockout results in the absence of endocri ne cells. This paper focuses on the question of whether these and other tra nscription factors, known to be necessary for pancreatic development, are a lso sufficient to drive a program of pancreatic organogenesis. Using in ovo electroporation of chick embryos, we show that ectopic expression of Pdx-1 or ngn3 causes cells to bud out of the epithelium like pancreatic progenit ors. The Pdx-1-expressing cells extinguish markers for other nonpancreatic regions of the endoderm and initiate, but do not complete, pancreatic cytod ifferentiation. Ectopic expression of ngn3 is sufficient to turn endodermal cells of any region into endocrine cells that form islets expressing gluca gon and somatostatin in the mesenchyme. The results suggest that simple gen e combinations could be used in stem cells to achieve specific endodermal t issue differentiation.