Molecular Mechanisms of Pancreas Development in Xenopus

• Applicant: Professor Dr. Tomas Pieler
• Subject Area: Developmental Biology
• Term: from 2004 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5430288

Molecular regulation of pancreas development in vertebrates is a topic of intense research activities, also because a better understanding of this process may lead to the definition of experimental protocols for the generation of pancreatic tissue from precursor cells in vitro, which could be employed in cell therapy of pancreas malfunction. During the past two years, we have worked out tools and protocols for the molecular analysis of liver and pancreas development, as well as for the induction of pancreas (and liver) gene expression in pluripotent embryonic precursor cells in Xenopus. We have also found retinoic acid (RA) to act as a key signal that is essentially reequired for the early endodermal patterning towards a pancreatic fate in Xenopus; furthermore, we observed that excessive RA promotes the formation of endocrine pancreatic cells at the expense of exocrine cells. In extension of these studies, we now intend to identify the RA-responcive genes that are involved in the patterning of the primitive endoderm. Furthermore, we wish to study the activity of three different transcription regulators, namely p48/Ptf1a, ESR-10 and ngnr1, in the context of endocrine-versus-exocrine pancreatic differentiation by use of gain- and loss-of-function approaches in transgenic frogs. We also intend to further advance our experimental protocol for the generation of endocrine and exocrine pancreatic cells from pluripotent embryonic precursor cells by employing relevant transcription regulators. Finally, we wish to define the transcriptome of purified, GFP-tagged pancreatic precursor cells by SAGE and microarray based approaches in order to identify novel candidate regulatory activities that are involved in early pancreas development.

• DFG Programme: Research Grants