The axial position of budding of the vertebrate pancreas from the embryonic foregut appears to be dependent upon cell-cell signaling pathways, and the TGFB family of signaling molecules plays an important role in the mediation of this process. Altering the level of developmental expression of at least three different TGFBs results in left/right reversals of the pancreas. In particular, overexpression of the Xenopus TGF B Xlefty alters heart and gut left/right development, including pancreatic positioning. Xlefty overexpression also results in a congenital defect known as annular pancreas, a condition in which the pancreas forms a constrictive ring around the duodenum. Furthermore, Xlefty is developmentally expressed in multiple sites implicated in pancreas formation.
The aim of this research is to define the role of Xlefty in the development and axial positioning of the pancreas. First, the developmental expression of Xlefty will be altered by overexpression and antisense depletion, and pancreatic development and positioning will be evaluated morphologically and with molecular markers. Second, following treatments that affect pancreatic development, Xlefty-expressing tissues will be examined molecularly to determine if perturbations in them correlate with changes in pancreatic development. Conversely, pancreatic development will be examined following extirpation of Xlefty expressing tissues. Lastly, the ability of Xlefty to affect endoderm and pancreatic development by modulating other TGFB signaling will be tested in animal cap and vegetal explant assays.
| Branford, William W; Yost, H Joseph (2002) Lefty-dependent inhibition of Nodal- and Wnt-responsive organizer gene expression is essential for normal gastrulation. Curr Biol 12:2136-41 |
