Development of multicellular organisms is regulated by highly complex transcriptional networks, which are synchronized by extra−cellular signaling cues. Whereas the functional role of transcription factors during organogenesis has been extensively elucidated, much less is known about how these factors are regulated by signals from the outside. A common theme during development of many organs is that epithelial and mesenchymal cells reciprocally regulate cellular behavior, such as cell proliferation, apoptosis, cell shape changes, cell migration, and cell differentiation.
We are particularly interested in how such cell−cell interactions regulate development of the pancreas, a gland consisting of endocrine (islets of Langerhans) and exocrine cells that originates from the foregut epithelium. We intend to investigate the nature and identity of the mesenchymal signals that regulate the differentiation and growth of the pancreatic epithelium. Moreover, we will decipher the effects of such signals on cell differentiation and morphogenesis of the pancreatic epithelium. Genome engineering in vivo and in vitro will be used for addressing the specific aims of this project.
The recent success in restoring normoglycemia in type 1 diabetes by islet cell transplantation and a severe lack of donor islets have created an increased demand for alternative sources for beta cells, such as embryonic stem (ES) cells. Thus, in addition to using the pancreas as a model organ for studying general principles of organogenesis, we will apply such knowledge to ongoing initiatives to direct differentiation of human ES cells towards pancreatic beta cells.
Last updated: March 18, 2009
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