A major interest of our Laboratory is to understand the genetic programs and molecular mechanisms that convert pluripotent stem cells of the vertebrate embryo into differentiated cell types. Our model organism is the zebrafish.

 In our research we employ molecular biological, genetic, bioinformatic and live-cell imaging approaches. 

In early vertebrate development TGF-beta (Transforming Growth Factor beta) signaling factors of the Nodal and BMP families have essential functions during formation and patterning of the three germ layers endoderm, mesoderm and ectoderm. The aim of our research is to understand how cells read this patterning signals and how cells translate these extrinsic signals into intrinsic cell differentiation programs. A major focus of our current studies is on the molecular and genetic interactions of the transcription factors FoxH1, Mixer and Ntl.

The pancreas is a vertebrate specific organ with essential functions in glucose regulation and food digestion. It consists of endocrine cell clusters, the islets, exocrine tissue surrounding the islets, and a duct system connecting exocrine and gut system. An important function of the endocrine cells is the production of insulin. Fish and mammals show a very similar pancreas architecture and use a highly conserved set of genes to control pancreas formation. Therefore the zebrafish is an ideal system for diabetes-related research.

We study the molecular control of endocrine differentiation and organ morphogenesis. A major focus is laid on the characterization fo the Hlxb9-related transcription factors Mnx1, Mnx2a and Mnx2b. These factors have conserved functions in pancreas formation and differentiation of insulin-producing β-cells. In addition, they are required for motoneuron differentiation and heterozygous loss of human Mnx1 is the major cause of sacral agenesis in patients suffering Currarino syndrome.

Selected Publications for "Control of Pancreas Formation and Regeneration"

Our work makes use of zebrafish diabetes models, as well as novel in vivo imaging modalities, to investigate the following:

• Requirement for diabetes-associated ion-channels in glucose-induced beta-cell excitability. We are also interested in the role of signaling between islet cell subtypes in maintaining glucose homeostasis, and changes that occur in diabetes.
• Long term impact of disrupted glucose homeostasis. We use zebrafish diabetes models to investigate tissue-specific changes in glucose transport and metabolism in susceptible tissues, and to define molecular mechanisms of organ pathologies.
• Metabolic response of beta cells to sustained glucose elevation. Our group is exploring how hyperglycemia induces oxidative stress and mitochondrial changes, leading to disruption of beta cell function and decreased survival.